THYMIC EPITHELIAL-CELL ABNORMALITIES IN (NZBXH-2(U))F1 MICE

Thymic maturation processes including MNC restriction and self-recogni tion require intimate association of thymocytes and stromal cells. Com pared to the thymic architecture of various ''normal'' control strains of mice, defects in the thymic microenvironment have been demonstrate d in New Zealand black (NZB) mice, Moreover, it is well known that NZB (H-d(d)) mice, when crossed with NZW(H-2(u)) mice, (NZB x NZW)F1, disp lay a unique spectrum of autoimmune disease manifestations, including murine SLE, Using an extensive panel of monoclonal antibodies that def ine the thymic microenvironment, we examined two additional strains of (NZB x H-2(u))F1 mice: (NZB x C57BL/10.PL)F1 and (NZB x PL/J)F1 mice to investigate the contributions of the 11-2 and non-H-2 loci to the t hymic abnormalities previously documented to occur in murine lupus. NZ B, NZW, and (NZB x NZW)F1 mice were studied concurrently as were two a dditional control strains C57BL/6 and C57BL/10Sn. NZW mice had a norma l thymic architecture as did the other H-2(u) mice and the control str ains. In contrast, (NZB x NZW)F1 mice had a significantly altered thym ic microenvironment; mild thymic abnormalities were also found in (NZB x PL/J)F1 but not in (NZB x CB7BL/10.PL)F1. As expected, (NZB x NZW)F 1 mice developed elevated titers of autoantibodies to DNA, proteinuria , and decreased life span. Interestingly, only (NZB x PL/J)F1 mice had increased levels of IgM antibodies to dsDNA, but did not manifest IgG anti-DNA or reduced survival, Defects in thymic stromal cells are ass ociated directly to autoimmunity and their origin appears to be determ ined by non-H-2 loci. (C) 1995 Academic Press, Inc.