Regulation of anti-Sm autoantibodies by the immunoglobulin heavy chain locus

Anti-Sm antibodies are specific markers for systemic lupus erythematosus in MRL mice and in humans. The prevalence of anti-Sm positivity in inbred MRL/Mp-lpr/lpr(MRL/lpr) mice is consistently about 25% at 5 mo of age, when the disease is at its peak. The control of the development of anti-Sm in individual MRL/lpr mice has been shown to be the result of stochastic factors, and previous research has indicated that the immunoglobulin heavy chain (IgH) b allotype may be more amenable to the production of anti-Sm. We have now further investigated the influence of the IgH genetic locus on the production of anti-Sm and other autoantibodies in an allotype congenic MRL strain, the MRL/Mp-Ipr/Ipr-IgHb (MRL/lpr-IgHb). Strikingly, 78% of MRL/lpr-IgHb mice produced anti-Sm, compared with 27% of contemporaneous MRL/lpr (IgHj) mice. Of those mice that were positive for anti-Sm, the MRL/lpr-IgHb strain produced significantly higher levels of anti-Sm than did the anti-Sm positive MRL/lpr mice. No differences were observed between the conventional MRL/lpr and the MRL/lpr-IgHb levels of antichromatin, anti-ssDNA, antiribosomal P, or anti-Su. In addition, kidney function, which was assessed by measuring serum urea nitrogen levels, was similar in the two strains. These results support the notion that the control of anti-Sm production in MRL/lpr mice operates through the IgH locus.