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Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses

The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studi...

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Autores principales: Kouskoff, Valerie, Famiglietti, Sara, Lacaud, Georges, Lang, Paul, Rider, James E., Kay, Brian K., Cambier, John C., Nemazee, David
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213405/
https://www.ncbi.nlm.nih.gov/pubmed/9782122
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author Kouskoff, Valerie
Famiglietti, Sara
Lacaud, Georges
Lang, Paul
Rider, James E.
Kay, Brian K.
Cambier, John C.
Nemazee, David
author_facet Kouskoff, Valerie
Famiglietti, Sara
Lacaud, Georges
Lang, Paul
Rider, James E.
Kay, Brian K.
Cambier, John C.
Nemazee, David
author_sort Kouskoff, Valerie
collection PubMed
description The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell–independent B cell proliferation, antibody secretion, induction of germline immunoglobulin γ1 transcripts, and B cell production of interleukin (IL) 2 and interferon γ responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40 signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at saturating ligand concentrations the ability of phage to stimulate some early signaling responses, such as Ca(++) mobilization and tyrosine phosphorylation of syk or Igα, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signaling by antigen determines whether an antibody response will be T independent or dependent is discussed.
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spelling pubmed-22134052008-04-16 Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses Kouskoff, Valerie Famiglietti, Sara Lacaud, Georges Lang, Paul Rider, James E. Kay, Brian K. Cambier, John C. Nemazee, David J Exp Med Articles The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell–independent B cell proliferation, antibody secretion, induction of germline immunoglobulin γ1 transcripts, and B cell production of interleukin (IL) 2 and interferon γ responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40 signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at saturating ligand concentrations the ability of phage to stimulate some early signaling responses, such as Ca(++) mobilization and tyrosine phosphorylation of syk or Igα, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest that the BCR is capable of differential signaling. The possibility that differential BCR signaling by antigen determines whether an antibody response will be T independent or dependent is discussed. The Rockefeller University Press 1998-10-19 /pmc/articles/PMC2213405/ /pubmed/9782122 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Kouskoff, Valerie
Famiglietti, Sara
Lacaud, Georges
Lang, Paul
Rider, James E.
Kay, Brian K.
Cambier, John C.
Nemazee, David
Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title_full Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title_fullStr Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title_full_unstemmed Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title_short Antigens Varying in Affinity for the B Cell Receptor Induce Differential B Lymphocyte Responses
title_sort antigens varying in affinity for the b cell receptor induce differential b lymphocyte responses
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213405/
https://www.ncbi.nlm.nih.gov/pubmed/9782122
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