Document Detail


Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in c1q-deficient mice.
MedLine Citation:
PMID:  17312136     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inherited deficiency of early components of the classical complement pathway is strongly associated with the targeting of intracellular self Ags in systemic lupus erythematosus, but the reasons for this association are debated. In this study, we show that C1q deficiency increases the positive selection of B1b B cells and IgM autoantibodies by an intracellular self Ag, which is exposed on dying cells, and decreases the negative selection of autoreactive conventional B cells by the same Ag. These effects are specific to intracellular Ag because C1q deficiency does not affect negative selection by extracellular self Ag or increase the positive selection of naive B cells. The B1-derived IgM autoantibody binds to the intracellular Ag when it is expressed on dying cells, leading to fixation of C1q and clearance of cells by phagocytosis. These findings suggest that the positive selection of autoreactive B1 cells by self Ags may contribute to the IgM and C1q-dependent clearance of dying cells in a feedback loop that limits exposure of conventional B cells to immunogenic self Ags. We show that exposure of intracellular Ag leads to the activation of conventional B cells, when there is a source of T cell help in vivo.
Authors:
Helen Ferry; Paul K Potter; Tanya L Crockford; Anastasia Nijnik; Michael R Ehrenstein; Mark J Walport; Marina Botto; Richard J Cornall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  178     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-21     Completed Date:  2007-04-24     Revised Date:  2007-08-13    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2916-22     Citation Subset:  AIM; IM    
Affiliation:
Henry Wellcome Building for Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantibodies / immunology
Autoantigens / genetics,  immunology*
B-Lymphocytes / immunology*,  pathology
Cell Death / genetics,  immunology
Complement C1q / deficiency*,  immunology
Immune Tolerance* / genetics
Immunoglobulin M / immunology
Lupus Erythematosus, Systemic / genetics,  immunology*,  pathology
Lymphocyte Activation / genetics,  immunology*
Mice
Mice, Knockout
Phagocytosis / genetics,  immunology
T-Lymphocytes / immunology,  pathology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Autoantigens; 0/Immunoglobulin M; 80295-33-6/Complement C1q

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