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Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production
Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewir...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478930/ https://www.ncbi.nlm.nih.gov/pubmed/23027925 http://dx.doi.org/10.1084/jem.20112744 |
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author | Jeelall, Yogesh S. Wang, James Q. Law, Hsei-Di Domaschenz, Heather Fung, Herman K.H. Kallies, Axel Nutt, Stephen L. Goodnow, Christopher C. Horikawa, Keisuke |
author_facet | Jeelall, Yogesh S. Wang, James Q. Law, Hsei-Di Domaschenz, Heather Fung, Herman K.H. Kallies, Axel Nutt, Stephen L. Goodnow, Christopher C. Horikawa, Keisuke |
author_sort | Jeelall, Yogesh S. |
collection | PubMed |
description | Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewiring of the signaling apparatus or if it can arise from a single molecular change. By introducing individual CARD11 mutations found in human lymphomas into antigen-activated mature B lymphocytes in mice, we find here that lymphoma-derived CARD11 mutations switch the effect of self-antigen from inducing B cell death into T cell–independent proliferation, Blimp1-mediated plasmablast differentiation, and autoantibody secretion. Our findings demonstrate that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells and that mutations in this switch represent a powerful initiator for aberrant B cell responses in vivo. |
format | Online Article Text |
id | pubmed-3478930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34789302013-04-22 Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production Jeelall, Yogesh S. Wang, James Q. Law, Hsei-Di Domaschenz, Heather Fung, Herman K.H. Kallies, Axel Nutt, Stephen L. Goodnow, Christopher C. Horikawa, Keisuke J Exp Med Brief Definitive Report Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewiring of the signaling apparatus or if it can arise from a single molecular change. By introducing individual CARD11 mutations found in human lymphomas into antigen-activated mature B lymphocytes in mice, we find here that lymphoma-derived CARD11 mutations switch the effect of self-antigen from inducing B cell death into T cell–independent proliferation, Blimp1-mediated plasmablast differentiation, and autoantibody secretion. Our findings demonstrate that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells and that mutations in this switch represent a powerful initiator for aberrant B cell responses in vivo. The Rockefeller University Press 2012-10-22 /pmc/articles/PMC3478930/ /pubmed/23027925 http://dx.doi.org/10.1084/jem.20112744 Text en © 2012 Jeelall et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Jeelall, Yogesh S. Wang, James Q. Law, Hsei-Di Domaschenz, Heather Fung, Herman K.H. Kallies, Axel Nutt, Stephen L. Goodnow, Christopher C. Horikawa, Keisuke Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title | Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title_full | Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title_fullStr | Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title_full_unstemmed | Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title_short | Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production |
title_sort | human lymphoma mutations reveal card11 as the switch between self-antigen–induced b cell death or proliferation and autoantibody production |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478930/ https://www.ncbi.nlm.nih.gov/pubmed/23027925 http://dx.doi.org/10.1084/jem.20112744 |
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