BREAKDOWN OF B-CELL TOLERANCE IN A MOUSE MODEL OF SYSTEMIC LUPUS-ERYTHEMATOSUS

Anti-DNA antibodies, specifically those that stain nuclei in a homogen ous nuclear (HN) fashion, are diagnostic of systemic lupus erythematos us (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy ch ain transgene that increases the frequency of anti-HN antibodies to ad dress whether their production in SLE is the consequence of a defect i n B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune -prone transgenic mice, but in MRL-lpr/lyr transgenic mice their Ig wa s evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specif ic B cells, and that MRL-lpr/lpr mice are defective in this process po ssibly because of the lpr defect in the fas gene.