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B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.

Publication ,  Journal Article
Hossain, MA; Anasti, K; Watts, B; Cronin, K; Derking, R; Groschel, B; Kane, AP; Edwards, RJ; Easterhoff, D; Zhang, J; Rountree, W; Ortiz, Y ...
Published in: Cell Rep
June 28, 2022

HIV-1 envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant [KD]) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD and whether B cells discriminate among proteins of similar affinities that bind with different kinetic rates. Here, we use a panel of Env proteins and Ramos B cell lines expressing immunoglobulin M (IgM) B cell receptors (BCRs) with specificity for CD4-binding-site broadly neutralizing antibodies to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD but on sensing of association rate and a threshold antigen-BCR half-life.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 28, 2022

Volume

39

Issue

13

Start / End Page

111021

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Receptors, Antigen, B-Cell
  • Immunoglobulin M
  • HIV-1
  • HIV Antibodies
  • Antigens, Viral
  • Antibodies, Neutralizing
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Hossain, M. A., Anasti, K., Watts, B., Cronin, K., Derking, R., Groschel, B., … Alam, S. M. (2022). B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates. Cell Rep, 39(13), 111021. https://doi.org/10.1016/j.celrep.2022.111021
Hossain, Md Alamgir, Kara Anasti, Brian Watts, Kenneth Cronin, Ronald Derking, Bettina Groschel, Advaiti Pai Kane, et al. “B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.Cell Rep 39, no. 13 (June 28, 2022): 111021. https://doi.org/10.1016/j.celrep.2022.111021.
Hossain MA, Anasti K, Watts B, Cronin K, Derking R, Groschel B, et al. B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates. Cell Rep. 2022 Jun 28;39(13):111021.
Hossain, Md Alamgir, et al. “B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.Cell Rep, vol. 39, no. 13, June 2022, p. 111021. Pubmed, doi:10.1016/j.celrep.2022.111021.
Hossain MA, Anasti K, Watts B, Cronin K, Derking R, Groschel B, Kane AP, Edwards RJ, Easterhoff D, Zhang J, Rountree W, Ortiz Y, Saunders K, Schief WR, Sanders RW, Verkoczy L, Reth M, Alam SM. B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates. Cell Rep. 2022 Jun 28;39(13):111021.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 28, 2022

Volume

39

Issue

13

Start / End Page

111021

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Receptors, Antigen, B-Cell
  • Immunoglobulin M
  • HIV-1
  • HIV Antibodies
  • Antigens, Viral
  • Antibodies, Neutralizing
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology