Regulatory CD4+ T Cells Promote B Cell Anergy in Murine Lupus

To prevent autoimmunity, anergy of autoreactive B cells needs to be maintained, together with the suppression of hyperactive B cells. We previously reported that CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) can directly suppress autoantibody- producing autoreactive B cells in systemic lupus erythematosus. In this article, we show that Tregs can also reduce the production of autoantibodies in (NZB Chi NZW) F-1 mouse lupus B cells by promoting B cell anergy, both in vitro and in vivo. This phenomenon associated with a reduction in Ca 2+ flux in B cells, and CTLA-4 blockade inhibited the effects of Tregs on anergic lupus B cells. These findings identify a new mechanism by which Tregs can control production of autoantibodies in lupus B cells and, more generally, B cell activity in physiopathological conditions.