To address whether B cells expressing a disease-associated autospeclficity are regulated In normal mice, we have established a rheumatoid factor (RF) transgenic model of autoimmunity, using V genes derived from an IgA anti-lgG2a RF isolated from an autoimmune MRU//pr mouse. As we wished to study Induction of tolerance during B cell development, we cloned the V_H gene Into an IgM expression vector. The RF we chose binds only lgG2a of the ‘a’ allotype (lgG2a) but not lgG2a^b allowing us to produce transgenic animals on IgH^a and lgH^b backgrounds, which either express or lack the self-antigen. Two transgenic lines were studied. Using mice which lack the self-antigen, we show by fluorescence activated cell sorting and hybrldoma analysis that the H and L transgenes are expressed to the exclusion of endogenous genes in most splenic B cells.In spite of good allellc exclusion, transgenic mice which are genetically capable of expressing lgG2a' have reduced but significant ( ˜50 _μ/tg/ml) serum levels. Nonetheless, the frequency and numbers of transgene-expressing B cells In peripheral lymphold organs of such mice which have the self-antigen are similar to those which lack It (lgH^b mice). Thus, B cells expressing an antiself lgG2a surface receptor can develop In this system. Whether such B cells are anerglc or otherwise regulated in autoantlgen-expressing mice Is discussed.