Signals that drive T-bet expression in B cells.

Transcription factors regulate various developmental and functional aspects of B cells. T-bet is a recently appreciated transcription factor associated with "Age-associated B cells" or ABCs, the development of autoimmunity, and viral infections. T-bet expression is favored by nucleic acid-containing antigens and immune complexes and is regulated by interplay between various cytokines, notably, the TFH cytokines IL-21, IL-4 and IFNγ. Adaptive signals by themselves cannot upregulate T-bet; however, they have a synergistic effect on induction of T-bet by innate receptors. The functional role of T-bet+ B cells is unclear, although it is known that T-bet promotes class switching to IgG2a/c. It is likely T-bet serves dichotomous roles in B cells, promoting pathogenic autoreactive antibodies on one hand but mediating microbial immunity on the other, making it a target of interest in both therapeutic and prophylactic settings.