THE YAA GENE-MEDIATED ACCELERATION OF MURINE LUPUS - YAA(-) T-CELLS FROM NON-AUTOIMMUNE MICE COLLABORATE WITH YAA(-CELLS TO PRODUCE LUPUS AUTOANTIBODIES IN-VIVO() B)

The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune res ponses in mice predisposed to lupus-like autoimmune disease. We have p reviously shown that a cognate interaction of T cells with B cells exp ressing the Yaa gene appears to be responsible for the accelerated pro duction of autoantibodies. To investigate whether T cells that provide help for autoantibody production by Yaa(+) B cells need to express th e 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 diff ering by the Thy-1 and Igh allotypes. We then determined autoantibody production following the selective elimination of T cells of Yaa(+) or igin by treating mice with allele-specific anti-Thy-1 monoclonal antib ody. Our results demonstrated that the selective production of autoant ibodies by Yaa(+) B cells in Yaa(+)-Ya(-) double bone marrow chimeras can be mediated as efficiently by T cells from non-autoimmune mice lac king the Yna gene as by T cells from autoimmune mice bearing the Yaa g ene. This indicates that T cells from nonautoimmune Yaa(-) mice are ca pable of providing help for autoimmune responses by collaborating with Yaa(+) B cells. These data thus strongly suggest that the Yna gene de fect is not functionally expressed in T cells, but only in B cells, an d contrast with parallel experiments in the Ipl model, in which defect s of the Fas antigen in both T and B cells are crucial for the Ipl gen e-mediated promotion of autoantibody production.