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 × NZW)F1 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.