T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance.

IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFNγ receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B cells, which, in turn, drives expression of CD11b and CD11c on B cells. T-bet/CD11b/CD11c positive B cells appear during antiviral responses and produce high titers of antiviral IgG2a antibodies that are critical for efficient viral clearance. The results thus demonstrate a previously unknown role for T-bet expression in B cells during viral infections. Moreover, the appearance of T-bet(+) B cells during antiviral responses and during autoimmunity suggests a possible link between these two processes.