| T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells. | |
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MedLine Citation:
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PMID: 18691914 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies. |
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Authors:
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Robin A Herlands; Sean R Christensen; Rebecca A Sweet; Uri Hershberg; Mark J Shlomchik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Immunity Volume: 29 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-08-14 Completed Date: 2008-11-18 Revised Date: 2009-06-08 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 249-60 Citation Subset: IM |
Affiliation:
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Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8035, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoantibodies / immunology Autoimmunity* B-Lymphocytes / immunology*, metabolism CD4-Positive T-Lymphocytes / immunology Chromatin / immunology, metabolism Lymphocyte Activation* Mice Mice, Inbred MRL lpr Mice, Knockout Myeloid Differentiation Factor 88 / metabolism Somatic Hypermutation, Immunoglobulin T-Lymphocytes / immunology*, metabolism Toll-Like Receptor 7 / immunology, metabolism* Toll-Like Receptor 9 / immunology, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P01-AI36529/AI/NIAID NIH HHS; P01-AR050256/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Chromatin; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Toll-Like Receptor 7; 0/Toll-Like Receptor 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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