Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome

Mice with a targeted disruption of the gene encoding a lymphoid-expressed o rphan G protein-coupled receptor, G2A, demonstrate a normal pattern of T an d B lineage differentiation through young adulthood. As G2A-deficient anima ls age, they develop secondary lymphoid organ enlargement associated with a bnormal expansion of both T and B lymphocytes. Older G2A-deficient mice (>1 year) develop a slowly progressive wasting syndrome, characterized by lymp hocytic infiltration into various tissues, glomerular immune complex deposi tion, and anti-nuclear autoantibodies. G2A-deficient T cells are hyperrespo nsive to TCR stimulation, exhibiting enhanced proliferation and a lower thr eshold for activation. Our findings demonstrate that G2A plays a critical r ole in controlling peripheral lymphocyte homeostasis and that its ablation results in the development of a novel, late-onset autoimmune syndrome.