CELL SELECTION AND ALLELIC EXCLUSION OF AN ANTI-DNA IG TRANSGENE IN MRL-IPR IPR MICE/

We have used an Ig transgene (V(H)3H9) that increases the frequency of anti-DNA autoantibodies to address whether the production of antinucl ear Abs in systemic lupus erythematosus is the consequence of a breakd own of B cell tolerance. We have shown that nonautoimmune mice regulat e anti-DNA B cells, and that lupus-prone MRL-lpr/lpr mice are defectiv e in this regulation. Here we show that a subset of anti-DNA B cells, namely those that stain nuclei in a homogeneous fashion, not only fail to be deleted in MRL-lpr/lpr mice, but undergo preferential clonal ex pansion. In addition, we describe a surprising finding: the V(H)3H9 tr ansgene is less efficient at inhibiting endogenous heavy chain gene re arrangement on the autoimmune-prone MRL-lpr/lpr genetic background tha n on the nonautoimmune BALB/c background.