Document Detail


T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells.
MedLine Citation:
PMID:  18691914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Robin A Herlands; Sean R Christensen; Rebecca A Sweet; Uri Hershberg; Mark J Shlomchik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Immunity     Volume:  29     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-14     Completed Date:  2008-11-18     Revised Date:  2014-09-03    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  249-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
P01 AI036529/AI/NIAID NIH HHS; P01 AR050256/AR/NIAMS NIH HHS; P01-AI36529/AI/NIAID NIH HHS; P01-AR050256/AR/NIAMS NIH HHS; R01 AI061090/AI/NIAID NIH HHS; R01 AI073722/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Chromatin; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Toll-Like Receptor 7; 0/Toll-Like Receptor 9
Comments/Corrections

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