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The Journal of Immunology, 2003, 170: 4826-4832.
Copyright © 2003 by The American Association of Immunologists

The Naive B Cell Repertoire Predisposes to Antigen-Induced Systemic Lupus Erythematosus

Chuansheng Wang1,*, Magi Khalil1,*, Jeffrey Ravetch{ddagger} and Betty Diamond2,*,{dagger}

Departments of * Microbiology and Immunology and {dagger} Medicine, Albert Einstein College of Medicine, Bronx, NY 10461; and {ddagger} The Rockefeller University, New York, NY 10021

It is clear that the development of an autoimmune disease usually depends on both a genetic predisposition and an environmental trigger. In this study, we demonstrate that BALB/c mice develop a lupus-like serology following immunization with a peptide mimetope of DNA, while DBA/2 mice do not. We further demonstrate that the critical difference resides within the B cell compartment and that the naive B cell repertoire of DBA/2 mice has fewer B cells specific for the DNA mimetope. Differences in the strength of B cell receptor signaling exist between these two strains and may be responsible for the difference in disease susceptibility. BALB/c mice possess more autoreactive cells in the native repertoire; they display a weaker response to Ag and exhibit less Ag-induced apoptosis of B cells. DBA/2 mice, in contrast, display a stronger B cell receptor signal and more stringent central tolerance. This correlates with resistance to lupus induction. Thus, the degree to which autoreactive B cells have been eliminated from the naive B cell repertoire is genetically regulated and may determine whether a nonspontaneously autoimmune host will develop autoimmunity following exposure to Ag.


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The JI 2003 170: 4423-4424. [Full Text]  



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