Skip to main content

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.

Publication ,  Journal Article
Han, S; Zheng, B; Dal Porto, J; Kelsoe, G
Published in: J Exp Med
December 1, 1995

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 established primary immune response induces massive apoptotic death in GC B cells, but not in clonally related populations of nonfollicular B lymphoblasts and plasmacytes. Cell death in GCs occurs predominantly among light zone centrocytes, is antigen specific, and peaks within 4-8 h after injection. Antigen-induced programmed death does not involve cellular interactions mediated by CD40 ligand (CD40L) or Fas; disruption of GCs by antibody specific for CD40L was not driven by apoptosis and C57BL/6.lpr mice, though unable to express the Fas death trigger, remained fully susceptible to soluble antigen. Single injections of antigen did not significantly decrease GC numbers or average size, but repeated injections during an 18-h period resulted in fewer and substantially smaller GCs. As cell loss appeared most extensive in the light zone, decreased GC cellularity after prolonged exposure to soluble antigen implies that the Ig- centroblasts of the dark zone may require replenishment from light zone cells that have survived antigenic selection. GC cell death is avidity-dependent; oligovalent antigen induced relatively little apoptosis and GC B cells that survived long exposures to multivalent antigen expressed atypical VDJ rearrangements unlikely to encode high affinity antibody. Antigen-induced apoptotic death in GCs may represent a mechanism for the peripheral deletion of autoreactive B cell mutants much as the combinatorial repertoire of immature B lymphocytes is censored in the bone marrow.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

December 1, 1995

Volume

182

Issue

6

Start / End Page

1635 / 1644

Location

United States

Related Subject Headings

  • Spleen
  • Phenylacetates
  • Nitrophenols
  • Molecular Sequence Data
  • Mice
  • Membrane Glycoproteins
  • Lymphocyte Cooperation
  • Immunology
  • Immunologic Memory
  • Immunohistochemistry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Han, S., B. Zheng, J. Dal Porto, and G. Kelsoe. “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.J Exp Med 182, no. 6 (December 1, 1995): 1635–44. https://doi.org/10.1084/jem.182.6.1635.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

December 1, 1995

Volume

182

Issue

6

Start / End Page

1635 / 1644

Location

United States

Related Subject Headings

  • Spleen
  • Phenylacetates
  • Nitrophenols
  • Molecular Sequence Data
  • Mice
  • Membrane Glycoproteins
  • Lymphocyte Cooperation
  • Immunology
  • Immunologic Memory
  • Immunohistochemistry