The genetics of autoantibody production in MRL/lpr lupus mice.

We have investigated the influence of background genes in the MRL strain, as compared to C57BL/6, on the induction of autoimmunity in homozygous lpr/lpr mice. We have concentrated on two autoantibodies, anti-Sm and anti-chromatin. The propensity to make anti-Sm is controlled by dominant genes from the MRL background. However, the prevalence of this response is under the control of additional recessive genes. The anti-chromatin response is found in both MRL/Mp-lpr/lpr and in C57BL/6-lpr/lpr mice, but it appears earlier and in higher titers in the former strain. This high responder effect is controlled by dominant genes. In F1 mice between these two strains, both anti-Sm and anti-chromatin antibodies preferentially use the b Igh allotype from the low responder B6/lpr parent. In addition, in the progeny of backcross of the F1 to the MRL/lpr strain, the production of both anti-Sm and anti-chromatin is linked to the b allotype. These results demonstrate the contribution of dominant genes from the MRL background on the induction of severe autoimmunity. They also suggest that the B6 background expresses an Igh allotype particularly amenable to autoantibody production, in spite of the relatively mild SLE-like syndrome in this strain.

Duke Scholars

Author David Stephen Pisetsky Medicine, Rheumatology and Immunology