The Yaa gene-dependent B-cell deficiency worsens the generalized lymphadenopathy and autoimmunity of C57BL/6-gld male mice.

The BXSB mice are unique among murine models for systemic lupus erythematosus in that males are much more severely affected than females. The BXSB male disease is associated with a Y-chromosome-linked gene, which is an autoimmunity accelerator gene (Yaa). The Yaa mutation affects the B-cell subset, which becomes hyper-responsive to T-cell signals. The Yaa mutation was combined to the generalized lymphadenopathy disease (gld) gene in order to know whether an additional intrinsic B-cell defect might enhance gld disease in the male mice. The B6-gld-Yaa male mice were shown to display earlier and exacerbated lymphoproliferative and autoimmune features. It appeared that the milder gld syndrome observed in B6-gld male mice with a normal Y-chromosome was dependent on the mechanisms of B-cell activation and that the B cells could also accelerate the lymphoproliferation and the differentiation of T cells into Thy-1+ B220+ cells.