© The Rockefeller University Press, 0022-1007/1997/4/1317/ $5.00
The Journal of Experimental Medicine, 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
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.
Address correspondence to Linda Spatz, Albert Einstein College of Medicine, Microbiology and Immunology, Forchheimer 405, Bronx, NY 10461.
This project is supported by National Institutes of Health grants AI40163 (L. Spatz) and AR42533 (B. Diamond) and grants from the New York Chapter of the Arthritis Foundation. Linda Spatz is a recipient of a Young Scholar Award granted by the New York Partnership in Arthritis Research of the Arthritis Foundation, New York Chapter.
1Abbreviations used in this paper: ds, double-stranded; FR1, framework 1; ss, single-stranded; V, variable region.

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