Anti-Sm autoantibodies in MRL mice: analysis of precursor frequency.

Individual MRL-lpr mice vary in their capacity to generate anti-Sm autoantibodies spontaneously. We have compared the frequency of B-cell precursors for this autoantibody in serologically negative and serologically positive MRL-lpr mice, and in normals. Anti-Sm precursors were present in a frequency of approximately 1 per 10-30,000 in spleen cell cultures from anti-Sm positive mice, but were undetectable when spleen cells from serologically negative MRL-lpr mice or from normal mice were examined. Despite LPS stimulation, neither IgM nor IgG precursors could be detected. In parallel cultures, in contrast, anti-DNA autoantibody precursors were readily detected. The results thus indicate that, for the lupus-specific autoantibodies, the absence of antibody in autoimmune mice reflects a deficit in precursor B lymphocytes rather than an active regulatory mechanism. It is suggested that the generation of anti-Sm may reflect a low-probability random event in the generation of B-cell diversity.