Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation.

An as-yet-unidentified mutation, Y-linked autoimmune acceleration (Yaa), is responsible for the accelerated development of lupus-like autoimmune syndrome in mice. In view of a possible role for Yaa as a positive regulator of BCR signaling, we have explored whether the expression of the Yaa mutation affects the development and activation of transgenic autoreactive B cells expressing either 4C8 IgM anti-RBC or Sp6 IgM anti-DNA. In this study, we show that the expression of the Yaa mutation induced a lethal form of autoimmune hemolytic anemia in 4C8 transgenic C57BL/6 mice, likely as a result of activation of 4C8 anti-RBC autoreactive B cells early in life.