LIGHT-CHAIN USAGE IN ANTI-DOUBLE-STRANDED DNA B-CELL SUBSETS - ROLE IN CELL FATE DETERMINATION

Two major mechanisms for the regulation of autoreactive B cells that a rise in the bone marrow are functional silencing (anergy) and deletion . Studies to date suggest that low avidity interactions between B cell s and autoantigen lead to B cell silencing, whereas high avidity inter actions lead to deletion. Anti-double stranded (ds) DNA antibodies rep resent a pathogenic autospecificity in Systemic Lupus Erythematosus (S LE). An understanding of their regulation is critical to an understand ing of SLE. We now demonstrate in a transgenic model in which mice exp ress the heavy chain of a potentially pathogenic anti-DNA antibody tha t antibody affinity for dsDNA does not alone determine the fate of ant i-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on Light chain usage. A ma jor 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.