H‐2‐linked control of the Yaa gene‐induced acceleration of lupus‐like autoimmune disease in BXSB mice

The accelerated development of lupus‐like autoimmune disease in male BXSB mice (H‐2b, I‐E−) is associated to the presence of a mutant gene, designated Yaa, located on their Ychromosome. To investigate whether the H‐2b haplotype and/or the lack of expression of I‐E molecules play any role in the Yaa‐linked acceleration of autoimmune disease, an I‐E+ BXSB.H‐2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H‐2d (I‐E+) strain to that of BXSB.H‐2b (I‐E−) and BXSB.H‐2b/d (I‐E+) heterozygous mice. Male BXSB.H‐2d (I‐E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both‐H‐2b and H‐2d haplotypes. However. BXSB.H‐2b/d (I‐E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H‐2b (I‐E−) male mice. These results indicate that the expression of I‐E molecules and consequent clonal deletion or anergy of I‐E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H‐2d (I‐E+) male mice. The finding that the Yaa gene‐induced acceleration of lupus‐like autoimmune disease is modulated by gene(s) within or closely linked to the H‐2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.