A search for common immunological abnormalities at the onset of murine lupus in two genetically different strains

Mice of the genetically different BXSB and MRL/lpr strains develop murine lupus spontaneously at about three months of age. Polyclonal B-cell activation is thought to play a major role in the development of the syndrome in each strains, but the immunological events which lead to this activation are not known. We therefore examined the immune characteristics of mice aged 10-16 weeks, at the onset of the disease. We found consistent abnormalities in the percentages of lymphocyte sub-populations in both male BXSB, and male and female MRL/lpr mice. In particular, the ratio of helper to suppressor/cytotoxic T cells was found to be significantly lower in male BXSB, and in male and female MRL/lpr mice than in normal, control, DBA2 mice. Significant increases in serum IgG and IgA concentrations, indicative of polyclonal B cell activation, were present in each strain. The histological appearance of the lymphoid organs and the functional responses to mitogen stimulation were, however, distinctly different. We conclude that defective immunoregulation is likely to be significant in the initiation of murine lupus, since it is detectable at the onset of disease in two genetically distinct strains. It may be associated, however, with different immunological phenomena in strains of different genetic backgrounds.