SELECTIVE ENHANCING EFFECT OF THE YAA GENE ON IMMUNE-RESPONSES AGAINST SELF AND FOREIGN ANTIGENS

The BXSB Y chromosome-linked mutant gene, Yaa, accelerates the progres sion of a lupus-like autoimmune syndrome only in mice that are predisp osed to autoimmune diseases. Unlike the lpr gene, which causes the def ects in the Fas antigen-mediating apoptosis, the autoimmune enhancing activity of the Yaa gene is selective, depending on autoantigens, and varies among lupus-prone mice. To obtain a better definition of the ro le of the Yaa gene in the acceleration of autoimmune disease, we have investigated immune responses to several foreign antigens to determine whether the Yaa gene is able to potentiate immune responses to foreig n antigens in a selective manner. We report here that the Yaa gene pot entiated immune responses against foreign antigens only in mice which are genetically (H-2-linked) low responding, but not high or non-respo nding. Moreover, studies on Yaa(+)-Yaa(-) double bone marrow chimeric mice revealed that B cells from Yaa(+) mice were selectively stimulate d to produce antibodies to low-responding antigen, human IgG, while bo th B cell populations similarly responded to high-responding antigen, ovalbumin. Our results suggest that first, the selective immune enhanc ing activity of the Yaa gene may be related to differences in the capa city of T helper cells specific for given self or foreign antigens; an d second, a specific cognate interaction of T helper cells with Yaa(+) B cells is apparently responsible for the selective enhancement of im mune responses to antigens, to which mice are genetically low respondi ng.