Expression of Heterozygous lpr Gene in MRL Mice.

Abstract

The presence of the homozygous 1pr gene (1pr/1pr) in MRL mice has been regarded as mandatory for the development of the early onset of lupus disease, T-cell dysfunctions, and polyclonal B-cell activation. Congeneic MRL mice lacking the 1pr gene (MRL +/+) display neither the lupus disease nor the immunological abnormalities within the first year of life. In this study we examined the cellular functions of MRL mice heterozygous at the 1pr locus. The results indicate that MRL mice heterozygous at the 1pr locus display intermediate delayed-type hypersensitivity compared with homozygous 1pr/1pr mice on the one hand and congeneic +/+ mice on the other hand. Furthermore, proliferative responses to concanavalin A, measured by uptake of [3H]thymidine, were signifcantly lower in MRL mice heterozygous at the 1pr locus than in +/+ mice, but significantly higher than in homozygous MRL 1pr/1pr mice. Polyclonal B-cell activation, assessed by measurement of frequencies of IgG-secreting spleen cells, a prominent feature in MRL 1pr/1pr mice, was significantly lower in 1pr/+ mice and totally absent in +/+ mice. Furthermore, spleen cells spontaneously secreting auto-antibodies were found in large numbers in MRL 1pr/1pr mice and in considerably lower but still significant numbers in heterozygous MRL +/1pr mice. In contrast, spleen cells from matched MRL +/+mice did not display any spontaneous autoantibody production. Taken together, these data provide evidence for immunomodulatory properties of the heterozygous 1pr gene.