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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
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.
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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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