The Yaa gene-mediated acceleration of murine lupus: Yaa(-) T cells from non-autoimmune mice collaborate with Yaa(+) B cells to produce lupus autoantibodies in vivo

The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune responses in mice predisposed to lupus-like autoimmune disease. We have previously shown that a cognate interaction of T cells with B cells expressing the Yaa gene appears to be responsible for the accelerated production of autoantibodies. To investigate whether T cells that provide help for autoantibody production by Yaa(+) B cells need to express the Yaa gene, we have made radiation bone marrow chimeras containing two sets of T and B cells from mice with or without the Yaa gene and differing by the Thy-1 and Igh allotypes. We then determined autoantibody production following the selective elimination of T cells of Yaa(+) origin by treating mice with allele-specific anti-Thy-1 monoclonal antibody. Our results demonstrated that the selective production of autoantibodies by Yaa(+) B cells in Yaa(+)-Ya(-) double bone marrow chimeras can be mediated as efficiently by T cells from non-autoimmune mice lacking the Yna gene as by T cells from autoimmune mice bearing the Yaa gene. This indicates that T cells from nonautoimmune Yaa(-) mice are capable of providing help for autoimmune responses by collaborating with Yaa(+) B cells. These data thus strongly suggest that the Yna gene defect is not functionally expressed in T cells, but only in B cells, and contrast with parallel experiments in the Ipl model, in which defects of the Fas antigen in both T and B cells are crucial for the Ipl gene-mediated promotion of autoantibody production.