J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/04/1317/10 $2.00
Volume 185, Number 7, April 7, 1997 1317-1326

Light Chain Usage in Anti-double-stranded DNA B Cell Subsets: Role in Cell Fate Determination

By Linda Spatz,^* Vladimir Saenko, Andrey Iliev, Lori Jones, Larisa Geskin, and Betty Diamond^*

From the ^* Department of Medicine, and  Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461

Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti-double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic crossreactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.

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