HYPERPROLIFERATION OF BXSB B-CELLS IS LINKED TO THE YAA ALLELE

Systemic lupus erythematosus is characterized by polyclonal B cell act ivation, the production of autoantibodies, and often by renal disease. Previous studies demonstrated that unfractionated B cells from severa l strains of mice with lupus hyperproliferate in culture when stimulat ed with lipopolysaccharide (LPS) or anti-IgM. We wished to further exa mine proliferation of resting B cells from the BXSB mouse model of lup us and mice with the Yaa allele, when activated with a number of stimu li. Our work demonstrates that: (1) resting B cells from mice containi ng the Yaa allele hyperproliferated compared to that seen with B cells from mice lacking the Yaa allele, (2) this hyperproliferation occurre d whether cells were stimulated with phorbol myristate acetate/ionomyc in, LPS, anti-IgM, or CD40L cross-linking, (3) this hyperproliferation is specific to B and not T cells. Taken together these data suggest t hat one mechanism by which the Yaa allele contributes to the accelerat ed onset of lupus in BXSB male mice is through its influence on B cell activation. (C) 1996 Academic Press, Inc.