The BXSB/MpJ (BXSB) murine strain (H-2b) spontaneously develops an autoimmune 
syndrome with features of systemic lupus erythematosus (SLE) that affects males 
much earlier than females. A mutant gene located on the BXSB Y chromosome, 
designated Yaa (Y chromosome-linked autoimmune acceleration), is responsible for 
the acceleration of the disease observed in male BXSB mice. Studies on H-2 
congenic and I-E transgenic mice have clearly demonstrated that the MHC class II 
genes play a crucial role in the development or protection of SLE. However, the 
MHC effect can be completely masked by the presence of the Yaa gene in mice with 
certain genetic backgrounds. It is intriguing that the Yaa gene effect is 
selective on autoimmune responses, varying in different lupus-prone mice. 
Studies on immune responses against foreign antigens have shown that the Yaa 
gene potentiates immune responses only against antigens to which mice are 
genetically (H-2-linked) low-responding, but not high-responding. Thus, the 
selective immune enhancing activity of the Yaa gene may be related to 
differences in the capacity of T helper cells specific for given antigens. 
Moreover, studies on Yaa(+)-Yaa- bone marrow cell chimeric mice have suggested 
that a specific cognate interaction of T helper cells with Yaa+ B cells is 
responsible for a selective enhancing effect of immune responses to foreign 
antigens as well as autoantigens. It is significant that unlike the lpr 
mutation, whose abnormality is associated with the capacity of the Fas antigen 
to mediate apoptosis, the Yaa gene by itself is unable to induce significant 
autoimmune responses in mice without apparent SLE background. This suggests that 
the molecular defect of the Yaa gene is likely to differ from that of the lpr 
gene, and that the Yaa gene effect requires the abnormal autosomal genome 
present in lupus-prone mice. Based on these findings, a possible molecular 
nature of the Yaa gene abnormality will be discussed.