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 erythe matosus in that males are much more severely affected than females. Th e BXSB male disease is associated with a Y-chromosome-linked gene, whi ch 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 disea se (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 lymphoproliferativ e and autoimmune features. It appeared that the milder gld syndrome ob served 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 a ccelerate the lymphoproliferation and the differentiation of T cells i nto Thy-1(+) B220(+) cells.