Scholars@Duke
Garnett H. Kelsoe

Garnett H. Kelsoe

James B. Duke Distinguished Professor of Immunology
Integrative Immunobiology
ghkelsoe@duke.edu
Room 2243 Duke@RTP, 27 Alexandria Way, Durham, NC 27703
Room 2243 Duke@RTP, 27 Alexandria Way, Durham, NC 27703

Selected Publications

Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin.

Journal Article Proc Natl Acad Sci U S A · January 2, 2024 Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against d ... Full text Link to item Cite

A new class of antibodies that overcomes a steric barrier to cross-group neutralization of influenza viruses.

Journal Article PLoS Biol · December 2023 Antibody titers that inhibit the influenza virus hemagglutinin (HA) from engaging its receptor are the accepted correlate of protection from infection. Many potent antibodies with broad, intra-subtype specificity bind HA at the receptor binding site (RBS). ... Full text Link to item Cite

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.

Journal Article Nature reviews. Immunology · March 2023 After nearly four decades of research, a safe and effective HIV-1 vaccine remains elusive. There are many reasons why the development of a potent and durable HIV-1 vaccine is challenging, including the extraordinary genetic diversity of HIV-1 and its compl ... Full text Cite

A non-neutralizing glycoprotein B monoclonal antibody protects against herpes simplex virus disease in mice.

Journal Article J Clin Invest · February 1, 2023 There is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, but for HSV this strategy has proven ineffective. Precli ... Full text Open Access Link to item Cite

Infant Antibody Repertoires during the First Two Years of Influenza Vaccination.

Journal Article mBio · December 20, 2022 The first encounter with influenza virus biases later immune responses. This "immune imprinting," formerly from infection within a few years of birth, is in the United States now largely from immunization with a quadrivalent, split vaccine (IIV4 [quadrival ... Full text Link to item Cite

Recall of B cell memory depends on relative locations of prime and boost immunization.

Journal Article Science immunology · May 2022 Immunization or microbial infection can establish long-term B cell memory not only systemically but also locally. Evidence has suggested that local B cell memory contributes to early local plasmacytic responses after secondary challenge. However, it is unc ... Full text Cite

Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5hiPD-1hi T follicular helper cells.

Journal Article Immunity · February 8, 2022 T follicular helper (Tfh) cells are defined by a Bcl6+CXCR5hiPD-1hi phenotype, but only a minor fraction of these reside in germinal centers (GCs). Here, we examined whether GC-resident and -nonresident Tfh cells share a common physiology and function. Flu ... Full text Link to item Cite

A cell-based multiplex immunoassay platform using fluorescent protein-barcoded reporter cell lines.

Journal Article Commun Biol · November 25, 2021 Multiplex immunoassays with acellular antigens are well-established based on solid-phase platforms such as the Luminex® technology. Cell barcoding by amine-reactive fluorescent dyes enables analogous cell-based multiplex assays, but requires multiple label ... Full text Open Access Link to item Cite

Continuous Culture of Mouse Primary B Lymphocytes by Forced Expression of Bach2.

Journal Article J Immunol · September 1, 2021 Stable, long-term culture of primary B lymphocytes has many potential scientific and medical applications, but remains an elusive feat. A major obstacle to long-term culture is that in vitro mitogens quickly drive B cells to differentiate into short-lived ... Full text Link to item Cite

A Prevalent Focused Human Antibody Response to the Influenza Virus Hemagglutinin Head Interface.

Journal Article mBio · June 29, 2021 Novel animal influenza viruses emerge, initiate pandemics, and become endemic seasonal variants that have evolved to escape from prevalent herd immunity. These processes often outpace vaccine-elicited protection. Focusing immune responses on conserved epit ... Full text Open Access Link to item Cite

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Journal Article Cell · May 27, 2021 Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (b ... Full text Open Access Link to item Cite

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Journal Article Science · January 8, 2021 Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency virus ... Full text Open Access Link to item Cite

Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells.

Journal Article Front Immunol · 2021 Antibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC ... Full text Open Access Link to item Cite

Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report.

Journal Article Am J Transplant · October 2020 The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment ... Full text Open Access Link to item Cite

Ideal Vaccines: Balancing B Cell Recruitment and Differentiation.

Journal Article Immunity · September 15, 2020 In this issue of Immunity, Kato et al. show that high-affinity vaccines targeting rare B cells capable of broadly protective antibody responses are not hindered by promotion of terminal plasmacytic differentiation. These findings provide new understanding ... Full text Link to item Cite

Tracing Self-Reactive B Cells in Normal Mice.

Journal Article J Immunol · July 1, 2020 BCR transgenic mice dominate studies of B cell tolerance; consequently, tolerance in normal mice expressing diverse sets of autoreactive B cells is poorly characterized. We have used single B cell cultures to trace self-reactivity in BCR repertoires across ... Full text Link to item Cite

Structure-Guided Molecular Grafting of a Complex Broadly Neutralizing Viral Epitope.

Journal Article ACS Infect Dis · May 8, 2020 Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a "universal" influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes ... Full text Link to item Cite

Immune checkpoint modulation enhances HIV-1 antibody induction.

Journal Article Nat Commun · February 19, 2020 Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immun ... Full text Open Access Link to item Cite

Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5.

Journal Article J Immunol · December 15, 2019 2F5 is an HIV-1 broadly neutralizing Ab that also binds the autoantigens kynureninase (KYNU) and anionic lipids. Generation of 2F5-like Abs is proscribed by immune tolerance, but it is unclear which autospecificity is responsible. We sampled the BCR repert ... Full text Link to item Cite

Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses.

Journal Article J Immunol · December 15, 2019 Virus-like particles (VLPs) provide a well-established vaccine platform; however, the immunogenic properties acquired by VLP structure remain poorly understood. In this study, we showed that systemic vaccination with norovirus VLP recalls human IgA respons ... Full text Link to item Cite

Minding the gap: The impact of B-cell tolerance on the microbial antibody repertoire.

Journal Article Immunol Rev · November 2019 B lymphocytes must respond to vast numbers of foreign antigens, including those of microbial pathogens. To do so, developing B cells use combinatorial joining of V-, D-, and J-gene segments to generate an extraordinarily diverse repertoire of B-cell antige ... Full text Link to item Cite

Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies.

Journal Article Nat Commun · August 28, 2019 Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope select ... Full text Link to item Cite

Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.

Journal Article Cell Host Microbe · June 12, 2019 Viral glycoproteins are under constant immune surveillance by a host's adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosyla ... Full text Link to item Cite

Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism.

Journal Article Cell · May 16, 2019 Vaccines to generate durable humoral immunity against antigenically evolving pathogens such as the influenza virus must elicit antibodies that recognize conserved epitopes. Analysis of single memory B cells from immunized human donors has led us to charact ... Full text Link to item Cite

Self-tolerance curtails the B cell repertoire to microbial epitopes.

Journal Article JCI Insight · May 16, 2019 Immunological tolerance removes or inactivates self-reactive B cells, including those that also recognize cross-reactive foreign antigens. Whereas a few microbial pathogens exploit these "holes" in the B cell repertoire by mimicking host antigens to evade ... Full text Link to item Cite

Autoreactivity profiles of influenza hemagglutinin broadly neutralizing antibodies.

Journal Article Sci Rep · March 5, 2019 Epitope-focused approaches for selective clonal induction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies for influenza virus and other rapidly evolving pathogens. The two conserved epitopes on the influenza hemagglutinin ... Full text Link to item Cite

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.

Journal Article Immunity · December 18, 2018 Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glyca ... Full text Link to item Cite

Macaque SHIV Induction of 2G12-like Broadly Neutralizing Antibodies

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design.

Journal Article Retrovirology · July 28, 2018 A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the HIV-1 envelope protein. In infected individuals, broadly neutralizing antibodies (bNAbs) ... Full text Link to item Cite

Germinal center responses to complex antigens.

Journal Article Immunol Rev · July 2018 Germinal centers (GCs) are the primary sites of antibody affinity maturation, sites where B-cell antigen-receptor (BCR) genes rapidly acquire mutations and are selected for increasing affinity for antigen. This process of hypermutation and affinity-driven ... Full text Link to item Cite

What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling.

Journal Article Cold Spring Harb Perspect Biol · May 1, 2018 Featured Publication A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have in ... Full text Link to item Cite

Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density.

Journal Article Nat Commun · March 2, 2018 Featured Publication B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, ... Full text Open Access Link to item Cite

Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires.

Journal Article Immunity · January 16, 2018 Featured Publication Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs) from the two grou ... Full text Link to item Cite

The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID.

Journal Article Adv Immunol · 2018 Featured Publication Activation-induced cytidine deaminase (AID) expression in the germinal center response drives the immunoglobulin class-switch recombination and V(D)J hypermutation necessary for efficacious, high-affinity antibody responses. That AID is expressed in develo ... Full text Link to item Cite

Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.

Journal Article Cell Rep · December 26, 2017 Rapidly evolving pathogens such as HIV or influenza can quickly mutate their antigenic profiles, reducing the efficacy of conventional vaccines. Despite this challenge, functionally required epitopes are highly conserved among heterologous viral strains an ... Full text Link to item Cite

Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.

Journal Article Nat Commun · November 23, 2017 A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4- ... Full text Open Access Link to item Cite

Role of germinal centers for the induction of broadly-reactive memory B cells.

Journal Article Curr Opin Immunol · April 2017 Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cr ... Full text Link to item Cite

Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.

Journal Article Sci Transl Med · March 15, 2017 A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in indu ... Full text Link to item Cite

BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.

Journal Article Cell Rep · February 14, 2017 Featured Publication Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell ant ... Full text Link to item Cite

Immunodominance of Antibody Recognition of the HIV Envelope V2 Region in Ig-Humanized Mice.

Journal Article J Immunol · February 1, 2017 In the RV144 gp120 HIV vaccine trial, decreased transmission risk was correlated with Abs that reacted with a linear epitope at a lysine residue at position 169 (K169) in the HIV-1 envelope (Env) V2 region. The K169 V2 response was restricted to Abs bearin ... Full text Link to item Cite

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

Journal Article Sci Immunol · January 27, 2017 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of di ... Full text Link to item Cite

Host controls of HIV broadly neutralizing antibody development.

Journal Article Immunol Rev · January 2017 Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been ma ... Full text Link to item Cite

High Resolution of Humoral Responses to HIV-1: determinism or chance?

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · 2017 Cite

HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.

Journal Article J Immunol · December 15, 2016 The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cro ... Full text Link to item Cite

Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.

Journal Article Immunity · November 15, 2016 Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, ... Full text Link to item Cite

Efficient Culture of Human Naive and Memory B Cells for Use as APCs.

Journal Article J Immunol · November 15, 2016 The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods for human B cell culture is the capacity to support mature B cell proliferation. We developed a culture method to suppo ... Full text Link to item Cite

Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.

Journal Article J Immunol · November 15, 2016 Featured Publication Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high-affinity, class-switched Abs. We hypothesized that proliferating B cells in GCs create a hypoxic microenvironment that governs their further different ... Full text Link to item Cite

An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability.

Journal Article Nat Microbiol · November 14, 2016 The induction by vaccination of broadly neutralizing antibodies (bNAbs) capable of neutralizing various HIV-1 viral strains is challenging, but understanding how a subset of HIV-infected individuals develops bNAbs may guide immunization strategies. Here, w ... Full text Link to item Cite

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21).

Journal Article Blood · October 6, 2016 Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin i ... Full text Link to item Cite

Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.

Journal Article Sci Immunol · July 29, 2016 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1-infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1-infected individuals who mad ... Full text Link to item Cite

Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.

Journal Article Sci Transl Med · April 27, 2016 Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used ... Full text Link to item Cite

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Journal Article Cell · April 7, 2016 Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived a ... Full text Link to item Cite

Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

Journal Article Immunity · March 15, 2016 Featured Publication Germinal center (GC) B cells evolve toward increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two comple ... Full text Link to item Cite

HIV-Host Interactions: Implications for Vaccine Design.

Journal Article Cell Host Microbe · March 9, 2016 Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of HIV type 1 (HIV-1), which is a consequence of its propensity to mutate to escape immune responses, along with host factors that prevent the elicitation of prot ... Full text Link to item Cite

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Journal Article Cell Rep · January 5, 2016 Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induc ... Full text Link to item Cite

Heavy-chain receptor editing unbound.

Journal Article Proc Natl Acad Sci U S A · February 24, 2015 Full text Link to item Cite

Polyreactivity and autoreactivity among HIV-1 antibodies.

Journal Article J Virol · January 2015 Featured Publication UNLABELLED: It is generally acknowledged that human broadly neutralizing antibodies (bNAbs) capable of neutralizing multiple HIV-1 clades are often polyreactive or autoreactive. Whereas polyreactivity or autoreactivity has been proposed to be crucial for n ... Full text Link to item Cite

TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation.

Journal Article PLoS One · 2015 Accumulating evidence indicates that the tuberous sclerosis complex 1 (TSC1), a tumor suppressor that acts by inhibiting mTOR signaling, plays an important role in the immune system. We report here that TSC1 differentially regulates mTOR complex 1 (mTORC1) ... Full text Open Access Link to item Cite

The Cellular and Molecular Biology of HIV-1 Broadly Neutralizing Antibodies

Chapter · January 1, 2015 Featured Publication Induction of neutralizing antibodies capable of protecting against human immunodeficiency virus 1 (HIV-1) infection is a key goal of HIV-1 vaccine development. The target of neutralizing antibodies is the HIV-1 envelope (Env) protein on the virion surface. ... Full text Cite

Natural IgM is produced by CD5- plasma cells that occupy a distinct survival niche in bone marrow.

Journal Article J Immunol · January 1, 2015 Featured Publication Natural IgM is constitutively present in the serum, where it aids in the early control of viral and bacterial expansions. Natural IgM also plays a significant role in the prevention of autoimmune disease by promoting the clearance of cellular debris. Never ... Full text Link to item Cite

Efficient culture of human naive and memory B cells

Conference JOURNAL OF IMMUNOLOGY · 2015 Cite

Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.

Journal Article Immunity · December 18, 2014 In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second v ... Full text Link to item Cite

Curiouser and curiouser: the role(s) of AID expression in self-tolerance.

Journal Article Eur J Immunol · October 2014 Aicda is crucial for antibody diversification by mediating Ig class-switch recombination, V(D)J hypermutation (SHM) and, in some species, gene conversion. Recently, evidence has accumulated to show that Aicda is expressed during B-cell development and that ... Full text Link to item Cite

Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.

Journal Article Cell Host Microbe · September 10, 2014 Featured Publication Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deleti ... Full text Link to item Cite

Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.

Journal Article Cell · July 31, 2014 Featured Publication Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study ... Full text Link to item Cite

Progress in HIV-1 vaccine development.

Journal Article J Allergy Clin Immunol · July 2014 The past 2 years have seen a number of basic and translational science advances in the quest for development of an effective HIV-1 vaccine. These advances include discovery of new envelope targets of potentially protective antibodies, demonstration that CD ... Full text Link to item Cite

Redemption of autoreactive B cells.

Journal Article Proc Natl Acad Sci U S A · June 24, 2014 Full text Link to item Cite

The origin of natural antibody

Conference JOURNAL OF IMMUNOLOGY · May 1, 2014 Link to item Cite

Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells.

Journal Article J Immunol · April 15, 2014 B cell activation leads to proliferation and Ab production that can protect from pathogens or promote autoimmunity. Regulation of cell metabolism is essential to support the demands of lymphocyte growth and effector function and may regulate tolerance. In ... Full text Link to item Cite

Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.

Journal Article J Immunol · April 1, 2014 Featured Publication We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved mammalian self-Ag, kynureninase, and that the development of B cells specific for the 2F5 epitope is constrained by immunological tolerance. These observations suggest that the ... Full text Link to item Cite

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.

Journal Article J Clin Invest · April 2014 Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnA ... Full text Link to item Cite

Immune System Regulation in the Induction of Broadly Neutralizing HIV-1 Antibodies.

Journal Article Vaccines (Basel) · March 2014 In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of H ... Full text Link to item Cite

IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.

Journal Article PLoS One · 2014 B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, ... Full text Open Access Link to item Cite

Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation.

Journal Article Front Immunol · 2014 Affinity maturation of the antibody response is a fundamental process in adaptive immunity during which B-cells activated by infection or vaccination undergo rapid proliferation accompanied by the acquisition of point mutations in their rearranged immunogl ... Full text Open Access Link to item Cite

A tribute to Michael S. Neuberger.

Journal Article J Clin Invest · January 2014 Full text Link to item Cite

Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.

Journal Article J Biol Chem · November 1, 2013 Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membran ... Full text Link to item Cite

The human fetal lymphocyte lineage: identification by CD27 and LIN28B expression in B cell progenitors.

Journal Article J Leukoc Biol · November 2013 Featured Publication CD27, a member of the TNFR superfamily, is used to identify human memory B cells. Nonetheless, CD27(+) B cells are present in patients with HIGM1 syndrome who are unable to generate GCs or memory B cells. CD27(+)IgD(+) fetal B cells are present in umbilica ... Full text Link to item Cite

Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages.

Journal Article J Immunol · November 1, 2013 Featured Publication Macrophages and dendritic cells (DC) are distributed throughout the body and play important roles in pathogen detection and tissue homeostasis. In tissues, resident macrophages exhibit distinct phenotypes and activities, yet the transcriptional pathways th ... Full text Link to item Cite

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

Journal Article Nature · April 25, 2013 Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide ... Full text Open Access Link to item Cite

Analysis of Broad Neutralizing B Cell Lineages to Guide HIV-1 Immunogen Design

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · April 1, 2013 Link to item Cite

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.

Journal Article J Exp Med · February 11, 2013 Featured Publication Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by i ... Full text Open Access Link to item Cite

Disparate adjuvant properties among three formulations of "alum".

Journal Article Vaccine · January 11, 2013 Aluminum adjuvants, commonly referred to as "alum," are the most widespread immunostimulants in human vaccines. Although the mechanisms that promote humoral responses to alum-adsorbed antigens are still enigmatic, alum is thought to form antigen depots and ... Full text Link to item Cite

Central B-cell tolerance mediated by Aicda and Myd88

Conference JOURNAL OF IMMUNOLOGY · 2013 Cite

HIV-1 gp120 vaccine induces affinity maturation in both new and persistent antibody clonal lineages.

Journal Article J Virol · July 2012 Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade ... Full text Link to item Cite

B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study.

Journal Article Nat Biotechnol · May 7, 2012 Featured Publication Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do p ... Full text Link to item Cite

Regulation of Central B-cell Tolerance by Aicda and Myd88

Conference JOURNAL OF IMMUNOLOGY · May 1, 2012 Link to item Cite

CD27+ Developing B Cells are Common in Human Fetal Liver

Conference Journal of Allergy and Clinical Immunology · February 2012 Full text Cite

Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.

Journal Article PLoS One · 2012 BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody respo ... Full text Open Access Link to item Cite

Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation.

Journal Article J Virol · November 2011 Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 b ... Full text Link to item Cite

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

Journal Article J Exp Med · October 24, 2011 Featured Publication The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we ... Full text Open Access Link to item Cite

Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors.

Journal Article J Virol · October 2011 V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificit ... Full text Link to item Cite

Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls.

Journal Article J Immunol · October 1, 2011 Featured Publication The HIV-1 broadly neutralizing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated that targeted expression of its VDJ rearrangement alone was sufficient to trigger a profound B cell developmental blockade in 2F5 ... Full text Link to item Cite

Activation-induced cytidine deaminase mediates central tolerance in B cells.

Journal Article Proc Natl Acad Sci U S A · July 12, 2011 Featured Publication The Aicda gene product, activation-induced cytidine deaminase (AID), initiates somatic hypermutation, class-switch recombination, and gene conversion of Ig genes by the deamination of deoxycytidine, followed by error-prone mismatch- or base-excision DNA re ... Full text Link to item Cite

Role of immune mechanisms in induction of HIV-1 broadly neutralizing antibodies.

Journal Article Curr Opin Immunol · June 2011 Featured Publication Although antibodies can be elicited by HIV-1 infection or immunization, those that are broadly neutralizing (bnAbs) are undetectable in most individuals, and when they do arise in HIV-1 infection, only do so years after transmission. Until recently, the re ... Full text Link to item Cite

Plexin-D1 is a novel regulator of germinal centers and humoral immune responses.

Journal Article J Immunol · May 15, 2011 Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for s ... Full text Link to item Cite

Impaired social recognition memory in recombination activating gene 1-deficient mice.

Journal Article Brain Res · April 6, 2011 The recombination activating genes (RAGs) encode two enzymes that play key roles in the adaptive immune system. RAG1 and RAG2 mediate VDJ recombination, a process necessary for the maturation of B- and T-cells. Interestingly, RAG1 is also expressed in the ... Full text Link to item Cite

AID expression during B-cell development: searching for answers.

Journal Article Immunol Res · April 2011 Expression of activation-induced cytidine deaminase (AID) by germinal center (GC) B cells drives the processes of immunoglobulin (Ig) somatic hypermutation (SHM) and class switch recombination (CSR) necessary for the generation of high affinity IgG serum a ... Full text Link to item Cite

Transcriptome analysis of mouse stem cells and early embryos

Chapter · January 1, 2011 Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that inc ... Cite

Aicda mediates central tolerance in B cells

Conference JOURNAL OF IMMUNOLOGY · 2011 Cite

Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.

Journal Article PLoS One · 2011 Featured Publication Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that is dependent on C/EBPβ. Here, we sho ... Full text Open Access Link to item Cite

H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

Journal Article PLoS One · 2011 BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal ... Full text Open Access Link to item Cite

A new guise for hyper-IgM syndrome.

Journal Article Blood · December 23, 2010 Full text Link to item Cite

Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region.

Journal Article Nat Struct Mol Biol · December 2010 Featured Publication The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41 membrane-proximal external region (MPER) with the rare, broadly neutralizing human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is non-neutralizing and do ... Full text Link to item Cite

Distinct granuloma responses in C57BL/6J and BALB/cByJ mice in response to pristane.

Journal Article Int J Exp Pathol · October 2010 Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in ... Full text Link to item Cite

Genetic regulation of pristane-induced oil granuloma responses.

Journal Article Int J Exp Pathol · October 2010 Oil granuloma (OG) induced by intraperitoneal injection of pristane represents a non-infectious granuloma. Oil granuloma has been characterized, but the regulation of its formation still remains unknown. To address this, we injected pristane into various m ... Full text Link to item Cite

Stromal cell independent B cell development in vitro: generation and recovery of autoreactive clones.

Journal Article J Immunol Methods · March 31, 2010 Featured Publication We describe and characterize a stromal cell independent culture system that efficiently supports pro-B cell to IgM+ B cell development with near normal levels of IgH and Igkappa diversity. Pro-B cells present in non-adherent bone marrow cells proliferate i ... Full text Link to item Cite

Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance.

Journal Article Proc Natl Acad Sci U S A · January 5, 2010 Featured Publication We previously reported that some of the rare broadly reactive, HIV-1 neutralizing antibodies are polyreactive, leading to the hypothesis that induction of these types of neutralizing antibody may be limited by immunologic tolerance. However, the notion tha ... Full text Link to item Cite

Aicda inhibits B-cell development

Conference JOURNAL OF IMMUNOLOGY · 2010 Cite

Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.

Journal Article PLoS One · October 6, 2009 The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is w ... Full text Link to item Cite

Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.

Journal Article J Immunol · September 1, 2009 Featured Publication Somatic hypermutation normally occurs as a consequence of the expression of activation-induced cytidine deaminase (AID) by Ag-activated, mature B cells during T cell-dependent germinal center responses. Nonetheless, despite their inability to express CD154 ... Full text Link to item Cite

HIV-1 envelope induces memory B cell responses that correlate with plasma antibody levels after envelope gp120 protein vaccination or HIV-1 infection.

Journal Article J Immunol · August 15, 2009 Successful vaccines (i.e., tetanus and diphtheria) can induce long-lived Ab levels that are maintained by bone marrow plasma cells and plasma Ab levels do not correlate with numbers of blood memory B cells. Destruction of CD4(+) T cells early in HIV-1 acut ... Full text Link to item Cite

Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

Journal Article PLoS Med · July 7, 2009 BACKGROUND: The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreove ... Full text Open Access Link to item Cite

Conserved cryptic recombination signals in Vkappa gene segments are cleaved in small pre-B cells.

Journal Article BMC Immunol · June 25, 2009 BACKGROUND: The cleavage of recombination signals (RS) at the boundaries of immunoglobulin V, D, and J gene segments initiates the somatic generation of the antigen receptor genes expressed by B lymphocytes. RS contain a conserved heptamer and nonamer moti ... Full text Link to item Cite

169 Why do so few Antibodies Neutralize HIV-1? Tests of the “Tolerance Hypothesis”

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · June 2009 Full text Cite

IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia.

Journal Article J Immunol · May 15, 2009 Featured Publication Infections and inflammation trigger neutrophilias that are supported by a hematopoietic program of accelerated granulopoiesis known as emergency granulopoiesis. The intrinsic factors that drive reactive neutrophilias and emergency granulopoiesis have been ... Full text Link to item Cite

Effects of acute and chronic inflammation on B-cell development and differentiation.

Journal Article J Invest Dermatol · February 2009 Recently, our understanding of hematopoiesis and the development of the immune system has fundamentally changed, leading to significant discoveries with important clinical relevance. Hematopoiesis, once described in terms of irreversible and discrete devel ... Full text Link to item Cite

Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice.

Journal Article J Immunol · January 1, 2008 Featured Publication CD20 mAb-mediated B cell depletion is an effective treatment for B cell malignancies and some autoimmune diseases. However, the full effects of B cell depletion on natural, primary, and secondary Ab responses and the maintenance of Ag-specific serum Ig lev ... Full text Link to item Cite

Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.

Journal Article J Exp Med · December 24, 2007 Featured Publication Receptor editing is believed to play the major role in purging newly formed B cell compartments of autoreactivity by the induction of secondary V(D)J rearrangements. In the process of immunoglobulin heavy (H) chain editing, these secondary rearrangements a ... Full text Open Access Link to item Cite

The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes.

Journal Article J Immunol · April 1, 2007 Two neutralizing human mAbs, 2F5 and 4E10, that react with the HIV-1 envelope gp41 membrane proximal region are also polyspecific autoantibodies that bind to anionic phospholipids. To determine the autoantibody nature of these Abs, we have compared their r ... Full text Link to item Cite

T-independent activation-induced cytidine deaminase expression, class-switch recombination, and antibody production by immature/transitional 1 B cells.

Journal Article J Immunol · March 15, 2007 Featured Publication Inflammation elicits a splenic lymphopoiesis of unknown physiologic significance but one that juxtaposes developing B cells and exogenous Ag. We show that immature and transitional 1 (immature/T1) B cells constitutively express activation-induced cytidine ... Full text Link to item Cite

Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.

Journal Article Blood · February 15, 2007 Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive). Evidence for a role of antigen i ... Full text Link to item Cite

V(D)J recombinase-mediated processing of coding junctions at cryptic recombination signal sequences in peripheral T cells during human development.

Journal Article J Immunol · October 15, 2006 V(D)J recombinase mediates rearrangements at immune loci and cryptic recombination signal sequences (cRSS), resulting in a variety of genomic rearrangements in normal lymphocytes and leukemic cells from children and adults. The frequency at which these rea ... Full text Link to item Cite

Outside influence: TLRs direct hematopoietic cell fates.

Journal Article Immunity · June 2006 Toll-like receptors (TLRs) modulate immune responses indirectly by promoting the efficacy of antigen presentation. In this issue of Immunity, Nagai et al. (2006) demonstrate that TLR signals also bias hematopoietic progenitor cells toward myelopoiesis dire ... Full text Link to item Cite

Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow.

Journal Article J Exp Med · June 6, 2005 Featured Publication The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte production by promoting granulopoiesis over lymphopoiesis, a response that supports the reactive neutrophilia that fol ... Full text Open Access Link to item Cite

Antibody polyspecificity and neutralization of HIV-1: a hypothesis.

Journal Article Hum Antibodies · 2005 Featured Publication HIV-1 has evolved many ways to evade protective host immune responses, thus creating a number of problems for HIV vaccine developers. In particular, durable, broadly specific neutralizing antibodies to HIV-1 have proved difficult to induce with current HIV ... Link to item Cite

Computational tools for understanding sequence variability in recombination signals.

Journal Article Immunol Rev · August 2004 The recombination signals (RSs) that guide V(D)J rearrangement are remarkably diverse. In mice, fewer than 16% of RSs carry consensus heptamers and nonamers and none also contain a consensus spacer sequence. It is increasingly clear that this variability r ... Full text Link to item Cite

Should we B-leavin' now?

Journal Article Nat Immunol · July 2004 Full text Link to item Cite

Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.

Journal Article J Exp Med · January 5, 2004 Featured Publication Inflammation removes developing and mature lymphocytes from the bone marrow (BM) and induces the appearance of developing B cells in the spleen. BM granulocyte numbers increase after lymphocyte reductions to support a reactive granulocytosis. Here, we demo ... Full text Open Access Link to item Cite

Transcriptome analysis of mouse stem cells and early embryos.

Journal Article PLoS Biol · December 2003 Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that inc ... Full text Link to item Cite

Therapeutic CD154 antibody for lupus: promise for the future?

Journal Article J Clin Invest · November 2003 Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by the production of pathogenic autoantibodies. A new study demonstrates that passive antibody specific for the TNF family member, CD154, ameliorates disease by ... Full text Link to item Cite

A functional analysis of the spacer of V(D)J recombination signal sequences.

Journal Article PLoS Biol · October 2003 Featured Publication During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination m ... Full text Open Access Link to item Cite

Enhanced differentiation of splenic plasma cells but diminished long-lived high-affinity bone marrow plasma cells in aged mice.

Journal Article J Immunol · February 1, 2003 In the present work, we have dissected the mechanisms responsible for the impaired humoral responses in aging. We found that there was a substantially higher level of Ab-forming cells in the spleens of aged mice than that of young controls. However, the nu ... Full text Link to item Cite

Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling.

Journal Article J Exp Med · January 20, 2003 Featured Publication The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we computed the position-wise informa ... Full text Open Access Link to item Cite

The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development.

Journal Article Immunity · November 2002 Featured Publication Previous in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice. We found that the core-RAG2-c ... Full text Link to item Cite

Very low affinity B cells form germinal centers, become memory B cells, and participate in secondary immune responses when higher affinity competition is reduced.

Journal Article J Exp Med · May 6, 2002 Featured Publication To understand the relationship between the affinity of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) mice were created. H50Gmu(a) and T1(V23)mu(a) mice express mu H chain transgene ... Full text Open Access Link to item Cite

Identification and utilization of arbitrary correlations in models of recombination signal sequences.

Journal Article Genome Biol · 2002 Featured Publication BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes perform poorly when positions in t ... Full text Open Access Link to item Cite

Spontaneous formation of germinal centers in autoimmune mice.

Journal Article J Leukoc Biol · October 2001 Featured Publication The mechanisms of autoantibody production are not well understood. Germinal centers (GC) may be important sites of immune disregulation in autoimmune diseases. In this study, we document the presence of spontaneous GC formation in the spleens of several au ... Link to item Cite

Definition of a novel cellular constituent of the bone marrow that regulates the response of immature B cells to B cell antigen receptor engagement.

Journal Article J Immunol · May 15, 2001 Previously we defined a Thy1(dull) bone marrow-derived cell population that regulated fate decisions by immature B cells after Ag receptor signaling. The microenvironmental signals provided by this cell population were shown to redirect the B cell Ag recep ... Full text Link to item Cite

A role for secondary V(D)J recombination in oncogenic chromosomal translocations?

Journal Article Adv Cancer Res · 2001 Featured Publication Chromosomal translocations are hallmarks of certain lymphoproliferative disorders. Indeed, in many leukemias and lymphomas, translocations are the transforming event that brings about malignancy. Recurrence of the immunoglobulin (Ig) and T-cell receptor (T ... Full text Link to item Cite

CD4+Thy1- thymocytes with a Th-type 2 cytokine response.

Journal Article Int Immunol · January 2001 We have identified a small subset of CD3(+), CD4(+), CD8(-) thymocytes that do not express Thy1 (CD90). This Thy1(-) subset represents 1-3.7% of the total number of thymocytes in a naive mouse. CD4(+)Thy1(-) thymocytes express high levels of CD3, intermedi ... Full text Link to item Cite

Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2.

Journal Article J Exp Med · November 6, 2000 Featured Publication The complement system enhances antibody responses to T-dependent antigens, but paradoxically, deficiencies in C1 and C4 are strongly linked to autoantibody production in humans. In mice, disruption of the C1qa gene also results in spontaneous autoimmunity. ... Full text Open Access Link to item Cite

Remembrance of things past.

Journal Article Nat Immunol · November 2000 Full text Link to item Cite

Regulation of humoral immune responses by CD21/CD35.

Journal Article Immunol Rev · August 2000 Before antigen-specific immunity arises, the complement system responds by activation through the classical and/or alternative pathways leading to the covalent deposition of complement fragments. Three models, not mutually exclusive, have been proposed to ... Full text Link to item Cite

Humoral immune responses in Cr2-/- mice: enhanced affinity maturation but impaired antibody persistence.

Journal Article J Immunol · May 1, 2000 Deficiency in CD21/CD35 by disruption of the Cr2 loci leads to impaired humoral immune responses. In this study, we detail the role of CD21/CD35 on Ab responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken gamma-globulin. Surprisingl ... Full text Link to item Cite

Studies of the humoral immune response.

Journal Article Immunol Res · 2000 The humoral immune response arises from a complex choreography of cells and molecules that interact to produce lasting and effective defenses against pathogens. For more than fifteen years, our laboratory has studied how humoral responses are initiated, ho ... Full text Link to item Cite

Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice.

Journal Article J Exp Med · August 2, 1999 Featured Publication The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-x ... Full text Open Access Link to item Cite

RAG2:GFP knockin mice reveal novel aspects of RAG2 expression in primary and peripheral lymphoid tissues.

Journal Article Immunity · August 1999 Featured Publication We generated mice in which a functional RAG2:GFP fusion gene is knocked in to the endogenous RAG2 locus. In bone marrow and thymus, RAG2:GFP expression occurs in appropriate stages of developing B and T cells as well as in immature bone marrow IgM+ B cells ... Full text Link to item Cite

V(D)J hypermutation and receptor revision: coloring outside the lines.

Journal Article Curr Opin Immunol · February 1999 At least three mechanisms increase potential genetic diversity in peripheral B lymphocytes: hypermutation, gene conversion and secondary V(D)J rearrangements. These diversifying activities were once believed to be strictly confined to the immunoglobulin lo ... Full text Link to item Cite

Antigen drives very low affinity B cells to become plasmacytes and enter germinal centers.

Journal Article J Immunol · November 15, 1998 Featured Publication In the first week of the primary immune response to the (4-hydroxy-3-nitrophenyl)acetyl (NP) hapten, plasmacytic foci and germinal centers (GCs) in C57BL/6 mice are comprised of polyclonal populations of B lymphocytes bearing the lambda1 L-chain (lambda1+) ... Link to item Cite

Predicted and inferred waiting times for key mutations in the germinal centre reaction: evidence for stochasticity in selection.

Journal Article Immunol Cell Biol · August 1998 The germinal centre reaction (GCR) is a fundamental component of the immune response to T-dependent antigens, during which the immunoglobulin (Ig) genes of B cells experience somatic hypermutation and selection. A maximum-likelihood method on DNA sequence ... Full text Link to item Cite

V(D)J hypermutation and DNA mismatch repair: vexed by fixation.

Journal Article Proc Natl Acad Sci U S A · June 9, 1998 Full text Link to item Cite

Dependence of germinal center B cells on expression of CD21/CD35 for survival.

Journal Article Science · April 24, 1998 Affinity-driven selection of B lymphocytes within germinal centers is critical for the development of high-affinity memory cells and host protection. To investigate the role of the CD21/CD35 coreceptor in B cell competition for follicular retention and sur ... Full text Link to item Cite

Immunoglobulin gene hypermutation in germinal centers is independent of the RAG-1 V(D)J recombinase.

Journal Article Immunol Rev · April 1998 Antigen-driven somatic hypermutation in immunoglobulin genes coupled with stringent selection leads to affinity maturation in the B-lymphocyte populations present in germinal centers. To date, no gene(s) has been identified that drives the hypermutation pr ... Full text Link to item Cite

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. V. Affinity maturation develops in two stages of clonal selection.

Journal Article J Exp Med · March 16, 1998 Featured Publication To examine the role of germinal centers (GCs) in the generation and selection of high affinity antibody-forming cells (AFCs), we have analyzed the average affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs and serum antibodies both during and a ... Full text Open Access Link to item Cite

Immunosenescence and germinal center reaction.

Journal Article Immunol Rev · December 1997 Dysfunction of the immune system in aged individuals includes at least two important factors: accumulation of immunocytes with reduced function and accumulation of lymphocyte clones with self-reactive potential. Coincidently, there is a profound reduction ... Full text Link to item Cite

V(D)J recombinase activity in a subset of germinal center B lymphocytes.

Journal Article Science · October 10, 1997 Featured Publication Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates the potential for immunoglobulin gene rearrangement and the generation of new antigen receptor specificities. Intermediate products of V(D)J recombinati ... Full text Link to item Cite

Distinctive characteristics of germinal center B cells.

Journal Article Semin Immunol · August 1997 A cardinal property of the immune system is its ability to respond to an antigen that was encountered years before with an accelerated and enhanced secondary response. The property of anamnestic reactions depends upon the formation of long-lived compartmen ... Full text Link to item Cite

Neoteny in lymphocytes: Rag1 and Rag2 expression in germinal center B cells.

Journal Article Science · December 20, 1996 The products of the Rag1 and Rag2 genes drive genomic V(D)J rearrangements that assemble functional immunoglobulin and T cell antigen receptor genes. Expression of the Rag genes has been thought to be limited to developmentally immature lymphocyte populati ... Full text Link to item Cite

Alternative pathways for the selection of antigen-specific peripheral T cells.

Journal Article Nature · November 21, 1996 Featured Publication In the thymus, maturing lymphocytes receive activation signals mediated by the T-cell antigen receptor (TCR) that either promote clonal survival (positive selection) or induce apoptosis (negative selection). This balance between life and death is mirrored ... Full text Link to item Cite

Gamma delta T cell help of B cells is induced by repeated parasitic infection, in the absence of other T cells.

Journal Article Curr Biol · October 1, 1996 BACKGROUND: gamma delta T cells, like alpha beta T cells, are components of all well-studied vertebrate immune systems. Yet, the contribution of gamma delta T cells to immune responses is poorly characterized. In particular, it has not been resolved whethe ... Full text Link to item Cite

T helper cells in murine germinal centers are antigen-specific emigrants that downregulate Thy-1.

Journal Article J Exp Med · September 1, 1996 After immunization, activated splenic T cells proliferate in periarteriolar lymphoid sheaths (PALS) and subsequently migrate to the lymphoid follicle where they enter nascent germinal centers. Analysis of TCR V(D)J gene rearrangements indicates extensive e ... Full text Open Access Link to item Cite

Regulation of the B cell response to T-dependent antigens by classical pathway complement.

Journal Article J Immunol · July 15, 1996 Mice deficient in complement components C3 (C3 -/-) and C4 (C4 -/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage (phi X174). Characterization of the deficient mice demonstrated a diminished level of peanut ag ... Link to item Cite

CD28 is required for germinal center formation.

Journal Article J Immunol · June 15, 1996 Previous studies have demonstrated that the T cell costimulatory molecule, CD28, is important in the development of humoral immunity. CD28-deficient mice exhibit defects in isotype switching and are more susceptible to pathogens that depend on an effective ... Link to item Cite

The germinal center: a crucible for lymphocyte selection.

Journal Article Semin Immunol · June 1996 Antigen first activates T and B lymphocytes in the T-cell areas of secondary lymphoid tissues where cognate- and costimulus-dependent proliferation expands the population of reactive lymphocytes. Selected T- and B-cell progeny from this population migrate ... Full text Link to item Cite

Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.

Journal Article J Exp Med · May 1, 1996 The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating ... Full text Link to item Cite

Antibody response to a T-dependent antigen requires B cell expression of complement receptors.

Journal Article J Exp Med · April 1, 1996 Several lines of evidence indicate that antibody responses to T-dependent antigens require complement receptors expressed on either B lymphocytes or follicular dendritic cells. We have used RAG-2 deficient blastocyst complementation to create mice specific ... Full text Link to item Cite

Life and death in germinal centers (redux).

Journal Article Immunity · February 1996 Full text Link to item Cite

Somatic diversification of antibody responses.

Journal Article J Clin Immunol · January 1996 Full text Link to item Cite

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. IV. Affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance.

Journal Article J Exp Med · December 1, 1995 Featured Publication Germinal centers (GCs) are the sites of antigen-driven V(D)J gene hypermutation and selection necessary for the generation of high affinity memory B lymphocytes. Despite the antigen dependence of this reaction, injection of soluble antigen during an establ ... Full text Open Access Link to item Cite

Ig VH hypermutation is absent in the germinal centers of aged mice.

Journal Article J Immunol · October 1, 1995 After injection with immunogenic conjugates of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP), two distinct B cell populations can be identified in the spleen during the primary response. One of these populations is specialized for Ab production; the othe ... Link to item Cite

Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

Journal Article J Immunol · July 15, 1995 Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-C ... Link to item Cite

The germinal center reaction.

Journal Article Immunol Today · July 1995 Full text Link to item Cite

Hypermutation in T cells questioned.

Journal Article Nature · May 25, 1995 Full text Link to item Cite

Facultative role of germinal centers and T cells in the somatic diversification of IgVH genes.

Journal Article J Exp Med · April 1, 1995 The development of memory B cells takes place in germinal centers (GC) of lymphoid follicles where antigen-driven lymphocytes undergo somatic hypermutation and affinity selection, presumably under the influence of helper T cells. However, the mechanisms th ... Full text Link to item Cite

The nude mutation results in impaired primary antibody repertoire.

Journal Article Eur J Immunol · February 1995 We have studied the effect of the nude mutation and/or T lymphocytes on the development of V gene germ-line repertoire in neonatal athymic (nu/nu) and euthymic (+/nu) littermates. A total of 2.35 x 10(6) and 1.47 x 10(6) B lymphocyte clones from nu/nu and ... Full text Link to item Cite

Skewed VH and V kappa gene family expression and pairing occurs among B lymphocytes in autoimmune motheaten mice.

Journal Article Autoimmunity · 1995 Motheaten mice homozygous for the recessive mev mutation develop a fatal immunodeficiency syndrome associated with hypergammaglobulinemia, thymic aplasia, production of autoantibodies and development of a severe lupus like systemic autoimmune disease. Most ... Full text Link to item Cite

Locus-specific somatic hypermutation in germinal centre T cells.

Journal Article Nature · December 8, 1994 Featured Publication Somatic hypermutation and affinity-driven selection of active immunoglobulin genes occur in germinal centres (GCs), resulting in the generation of high-affinity memory B cells. In contrast, T lymphocytes do not require the germinal centre microenvironment ... Full text Link to item Cite

Lack of B7-2 expression in the germinal centers of aged mice

Journal Article Aging: Immunology and Infectious Disease · December 1, 1994 The humoral immune response is known to be depressed in the aged mouse. This immunodeficiency is associated with an impairment in the formation of germinal centers, the anatomic site of antibody affinity maturation and memory B cell generation. The formati ... Cite

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells.

Journal Article J Exp Med · October 1, 1993 Featured Publication In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were ... Full text Open Access Link to item Cite

Pairing of VH gene families with the lambda 1 light chain: evidence for a non-stochastic association.

Journal Article Eur J Immunol · August 1993 The frequencies at which four VH gene families pair with the lambda 1 light (L) chain were determined by sequential hybridization of VH- and lambda 1-specific DNA probes to mitogen-induced colonies of B cells. Analysis of pair frequencies indicates that th ... Full text Link to item Cite

Sites of B-cell activation in vivo.

Journal Article Curr Opin Immunol · June 1993 Novel techniques have made possible in situ analyses of the lymphocyte populations responding to antigen. In the spleen, antigen-specific T and B cells are first observed in the periarteriolar lymphoid sheath. Following conjugate formation between specific ... Full text Link to item Cite

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers.

Journal Article J Exp Med · September 1, 1992 Featured Publication In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-bi ... Full text Open Access Link to item Cite

Aging and humoral immunity.

Journal Article Md Med J · July 1992 If human antibody responses undergo molecular shifts similar to those identified in mice, the appropriate immunization strategy for the elderly would be a passive administration of the protective antibody from young donors rather than an attempt to boost t ... Link to item Cite

Intraclonal generation of antibody mutants in germinal centres.

Journal Article Nature · December 5, 1991 Featured Publication The generation and selection of somatic antibody mutants are key elements of acquired immunity, essential for the affinity maturation of antibody responses dependent on T cells. The mutants are generated through a mechanism that introduces point mutations ... Full text Link to item Cite

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations.

Journal Article J Exp Med · May 1, 1991 Featured Publication After primary immunization with an immunogenic conjugate of (4-hydroxy-3-nitrophenyl)acetyl, two anatomically and phenotypically distinct populations of antibody-forming cells arise in the spleen. As early as 2 d after immunization, foci of antigen-binding ... Full text Open Access Link to item Cite

Contribution of the VH11 gene family to mitogen-responsive B cell repertoire in C57BL/6 mice.

Journal Article Eur J Immunol · March 1991 The contribution of VH11 gene family to the development of the primary B cell repertoire has been studied by analyzing 1.8 x 10(4) mitogen induced B lymphocyte colonies. The data demonstrate that VH11 family is predominantly expressed among neonatal spleni ... Full text Link to item Cite

Cloning of murine splenic T lymphocytes and natural killer (NK) cells on filter paper discs: detection of a novel NK/T phenotype.

Journal Article Eur J Immunol · March 1991 Discrete colonies of splenocytes were grown on filter paper discs in the presence of concanavalin A and interleukin 2. Phenotypic analysis of the colonies indicated that the majority expressed the Thy-1.2 marker and 72% of these co-expressed the CD3 molecu ... Full text Link to item Cite

Stochastic pairing of heavy-chain and kappa light-chain variable gene families occurs in polyclonally activated B cells.

Journal Article Proc Natl Acad Sci U S A · July 1990 Featured Publication Frequencies of 25 immunoglobulin heavy-chain and kappa light-chain variable (VH + V kappa) gene-family pairings expressed in splenic B-cell populations were determined by hybridization of VH- and V kappa-family-specific DNA probes to mitogen-induced B-cell ... Full text Link to item Cite

Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice.

Journal Article J Immunol · March 1, 1990 LPS-stimulated B cells were used to generate a panel of mAb that were a random sample of the preimmune repertoire of C57BL/6 and highly autoimmune, viable motheaten mice. These mAb were tested for reactivity to a number of "self" and foreign Ag. Binding th ... Link to item Cite

Murine V kappa gene expression does not follow the VH paradigm.

Journal Article J Exp Med · May 1, 1989 Featured Publication V kappa gene family expression among LPS-reactive murine B lymphocytes, unlike that of VH gene families, is not proportional to genomic complexity, i.e., nonstoichiometric. Furthermore, no positional bias for the overexpression of J-proximal V kappa genes ... Full text Open Access Link to item Cite

Mapping of antibody specificities to VH gene families.

Journal Article Immunogenetics · 1989 VH gene segments represent the products of the repeated duplication and subsequent diversification of a primordial V gene element. It is widely assumed that natural selection, operating via pathogens, has played the dominant role in this process. Here, we ... Full text Link to item Cite

Genotypic analysis of B cell colonies by in situ hybridization. Stoichiometric expression of three VH families in adult C57BL/6 and BALB/c mice.

Journal Article J Exp Med · July 1, 1987 Featured Publication The filter paper disc method for cloning inducible lymphocytes was used to census the splenic B cell population of C57BL/6 and BALB/c mice for the expression of three VH gene-families, VH X-24, -Q52, and -J558. B cell colonies, arising from single founder ... Full text Open Access Link to item Cite

Cloning of mitogen- and antigen-reactive B lymphocytes on filter paper discs. II. Paratope frequencies within the mitogen-selected repertoire.

Journal Article Cell Immunol · April 1, 1986 Paratopic frequencies of C57BL/6 (Igh-Vb) and BALB/c (Igh-Va) mice were compared by determining the frequency of lipopolysaccharide-reactive, splenic B lymphocytes secreting antibody specific for (4-hydroxy-5-iodo-3-nitrophenyl) acetyl (NIP), trinitropheny ... Full text Link to item Cite

Regulation of the immune response. II. Concomitant idiotope-specific enhancement and suppression can result in a phenotypically normal response.

Journal Article Cell Immunol · March 1986 Idiotope-specific immunoenhancement or suppression was induced in C57BL/6 mice by the injection of physiological amounts (100 ng-10 micrograms) of monoclonal anti-idiotope antibody. As previously described, nanogram doses enhanced idiotope expression while ... Full text Link to item Cite

Cloning of mitogen- and antigen-reactive B lymphocytes on filter paper discs. I. A description of the technique and of methods for the analysis of colonies.

Journal Article J Immunol Methods · February 11, 1985 A novel technique for establishing short term clones of antigen- or mitogen-activated splenic B lymphocytes is described. Spleen cells are plated onto the surface of filter paper discs and subsequently stimulated by antigen or mitogen in situ; activated B ... Full text Link to item Cite

Network interactions, 1983.

Journal Article Surv Immunol Res · 1984 Full text Link to item Cite

Priority of the anti-idiotypic response after antigen administration: artefact or intriguing network mechanism?

Journal Article Immunology Today · January 1, 1984 Immunization triggers at least two speck responses measurable at cellular and humoral levels: the antigen-driven proliferation of idiotype-bearing (idt+) cells; and an autochthonous anti-idt response'. As the expansion of the idt* clone(s) is presumed to p ... Full text Cite

Control of idiotope expression by monoclonal anti-idiotope and idiotope-bearing antibody.

Journal Article Eur J Immunol · May 1981 Preinjection of C57BL/6 mice with nano-to microgram amounts of a monoclonal IgG1 antibody directed against a binding site-related idiotope of the anti-NP [(4-hydroxy-3-nitro-phenyl)acetyl] antibody B1-8 results in enhancement or suppression of the correspo ... Full text Link to item Cite

Idiotypic regulation by isologous monoclonal anti-idiotope antibodies.

Journal Article Nature · March 19, 1981 Featured Publication Full text Link to item Cite

Thymic requirement for cyclical idiotypic and reciprocal anti-idiotypic immune responses to a T-independent antigen.

Journal Article J Exp Med · February 1, 1980 Featured Publication The role of the thymus in the cyclical appearance of the dominant idiotype of the myeloma protein secreted by the TEPC-15 plasmacytoma (T-15)-bearing plaque-forming cells (PFC) and anti-idiotypic cells (i.e., cells with receptors for T-15) in the spleen du ... Full text Open Access Link to item Cite

Immunodiagnosis of infection with Schistosoma mansoni: enzyme-linked immunosorbent assay for detection of antibody to circulating antigen.

Journal Article Proc Natl Acad Sci U S A · November 1978 Featured Publication A circulating antigen, a negatively charged polysaccharide from the trematode Schistosoma mansoni, was noncovalently bound to the surface of poly(L-lysine)-coated wells in polystyrene trays, which were then used in a micro-enzyme-linked immunosorbent assay ... Full text Link to item Cite

Regulation of the immune response. I. Regulatory cell equilibrium in the "virgin" state.

Journal Article Eur J Immunol · March 1978 Spleen cells from pairs of inbred mice (age- and sex-matched) were challenged in vitro with a T-independent antigen. The specific plaque-forming cell (PFC) response in cultures containing cells from both donors was not intermediate to the responses of inde ... Full text Link to item Cite

The fine structure of spermatogenesis in Hymenolepis diminuta (Cestoda) with a description of the mature spermatozoon.

Journal Article Z Parasitenkd · December 27, 1977 The processes of spermatogenesis and spermiogenesis in Hymenolepis diminuta were studied by electron microscopy using improved preparative techniques. Spermatogonia (Type A) are characterized by nuclei 3.79 (+/- 0.17) micrometer in diameter, dense cytoplas ... Full text Link to item Cite

FINE MORPHOLOGY OF SPERMATOGENESIS IN HYMENOLEPIS-DIMINUTA (CESTODA)

Conference TEXAS REPORTS ON BIOLOGY AND MEDICINE · 1973 Cite

ELECTRON-MICROSCOPY OF SPERMATOGENESIS IN HYMENOLEPIS-DIMINUTA (CESTODA)

Conference TEXAS REPORTS ON BIOLOGY AND MEDICINE · 1972 Cite