International Immunology, Vol. 12, No. 3, 353-364,
March 2000
© 2000 Japanese Society for Immunology
The origin of anti-nuclear antibodies in bcl-2 transgenic mice
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
1 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Correspondence to: J. Erikson
bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, 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 shown that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA B cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of B cell anergy; rather they may originate from B cells that have transited through a germinal center.
Keywords: anti-nuclear antibodies, apoptosis, autoimmunity, germinal center, tolerance
Transmitting editor: D. Tarlinton
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