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 progression of a lupus-like autoimmune syndrome only in mice that are predisposed to autoimmune diseases. Unlike the lpr gene, which causes the defects 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 role 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 foreign antigens in a selective manner. We report here that the Yaa gene potentiated immune responses against foreign antigens only in mice which are genetically (H-2-linked) low responding, but not high or non-responding. Moreover, studies on Yaa⁺-Yaa^? double bone marrow chimeric mice revealed that B cells from Yaa⁺ mice were selectively stimulated to produce antibodies to low-responding antigen, human IgG, while both B cell populations similarly responded to high-responding antigen, ovalbumin. Our results suggest that first, the selective immune enhancing activity of the Yaa gene may be related to differences in the capacity of T helper cells specific for given self or foreign antigens; and second, a specific cognate interaction of T helper cells with Yaa⁺ B cells is apparently responsible for the selective enhancement of immune responses to antigens, to which mice are genetically low responding.