The origin of anti-nuclear antibodies in bcl-2 transgenic mice

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies simi lar to those present in systemic lupus erythematosus. To begin to understan d where a breakdown in the regulation of autoreactive lymphocytes is occurr ing, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have sho wn that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifes ted by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice in creased the lifespan of anti-dsDNA B cells, but did not alter the other fea tures of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest tha t the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of a cell anergy; rather they ma y originate from a cells that have transited through a germinal center.