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B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly und...
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/PMC3348102/ https://www.ncbi.nlm.nih.gov/pubmed/22547654 http://dx.doi.org/10.1084/jem.20111675 |
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author | Barr, Tom A. Shen, Ping Brown, Sheila Lampropoulou, Vicky Roch, Toralf Lawrie, Sarah Fan, Boli O’Connor, Richard A. Anderton, Stephen M. Bar-Or, Amit Fillatreau, Simon Gray, David |
author_facet | Barr, Tom A. Shen, Ping Brown, Sheila Lampropoulou, Vicky Roch, Toralf Lawrie, Sarah Fan, Boli O’Connor, Richard A. Anderton, Stephen M. Bar-Or, Amit Fillatreau, Simon Gray, David |
author_sort | Barr, Tom A. |
collection | PubMed |
description | B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS. |
format | Online Article Text |
id | pubmed-3348102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33481022012-11-07 B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells Barr, Tom A. Shen, Ping Brown, Sheila Lampropoulou, Vicky Roch, Toralf Lawrie, Sarah Fan, Boli O’Connor, Richard A. Anderton, Stephen M. Bar-Or, Amit Fillatreau, Simon Gray, David J Exp Med Article B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS. The Rockefeller University Press 2012-05-07 /pmc/articles/PMC3348102/ /pubmed/22547654 http://dx.doi.org/10.1084/jem.20111675 Text en © 2012 Barr 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 | Article Barr, Tom A. Shen, Ping Brown, Sheila Lampropoulou, Vicky Roch, Toralf Lawrie, Sarah Fan, Boli O’Connor, Richard A. Anderton, Stephen M. Bar-Or, Amit Fillatreau, Simon Gray, David B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title | B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title_full | B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title_fullStr | B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title_full_unstemmed | B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title_short | B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells |
title_sort | b cell depletion therapy ameliorates autoimmune disease through ablation of il-6–producing b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348102/ https://www.ncbi.nlm.nih.gov/pubmed/22547654 http://dx.doi.org/10.1084/jem.20111675 |
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