| Synovial fibroblasts promote immunoglobulin class switching by a mechanism involving BAFF. | |
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MedLine Citation:
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PMID: 21557212 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Fibroblast-like synoviocytes (FLS) are important actors in rheumatoid arthritis (RA) pathogenesis. The autoimmune nature of RA is attributed to autoantibody production, which confers to B cells a predominant role in RA. Several arguments support an induction of class switch recombination (CSR) process in RA synovium, causing (in conjunction with somatic hypermutation) the production of potentially pathogenic IgG. To determine whether RA FLS can directly promote CSR and to analyze the role of external factors like TLR signals and BAFF family cytokines in this FLS-B cell crosstalk, we performed cocultures of blood B cells (from normal individuals or RA patients) with RA FLS and analyzed CSR induction by quantification of AICDA (encoding activation induced cytidine deaminase, AID) and switch circular transcripts expression, and IgG secretion. RA FLS (and to a lesser extent osteoarthritis or control FLS) promoted CSR, and TLR3 stimulation potentialized it. In addition, induction of CSR by RA FLS was totally dependent on cell-cell contact in basal conditions, and partially dependent in the case of TLR3 stimulation. Finally, we showed that the mechanism by which RA FLS induce CSR is mostly BAFF-dependent. Our results support the hypothesis that CSR can be induced outside the ectopic lymphoid structures in RA. |
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Authors:
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Ghada Alsaleh; Antoine François; Anne-Marie Knapp; Jean-Nicolas Schickel; Jean Sibilia; Jean-Louis Pasquali; Jacques-Eric Gottenberg; Dominique Wachsmann; Pauline Soulas-Sprauel |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-10 |
Journal Detail:
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Title: European journal of immunology Volume: - ISSN: 1521-4141 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Laboratoire Physiopathologie des Arthrites, EA4438, Université de Strasbourg, UFR Sciences Pharmaceutiques, Illkirch, France, and Departement de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg Hautepierre, France. |
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