T-bet+ memory B cells: Generation, function, and fate

B cells expressing the transcription factor T-bet have emerged as participants in a number of protective and pathogenic immune responses. T-bet(+) B cells characteristically differentiate in response to combined Toll-like receptor and cytokine signaling, contribute to protective immunity against intracellular pathogens via IgG2(a/c) production and antibody-independent mechanisms, and are prone to produce autoantibodies. Despite recent advances, a number of questions remain regarding the basic biology of T-bet(+) B cells and their functional niche within the immune system. Herein, we review the discovery and defining characteristics of the T-bet(+) B cell subset in both mice and humans. We further discuss their origins, the basis for their persistence, and their potential fate in vivo. Evidence indicates that T-bet(+) B cells represent a distinct, germinal center-derived memory population that may serve as an important therapeutic target for the improvement of humoral immunity and prevention of autoimmunity.