Age-Associated B Cells: A T-bet-Dependent Effector with Roles in Protective and Pathogenic Immunity

Abstract

A newly discovered B cell subset, age-associated B cells, expresses the transcription factor T-bet, has a unique surface phenotype, and accumulates progressively with age. Moreover, B cells with these general features are associated with viral infections and autoimmunity in both mice and humans. In this article, we review current understanding of the characteristics, origins, and functions of these cells. We also suggest that the protective versus pathogenic actions of these cells reflect appropriate versus aberrant engagement of regulatory mechanisms that control the Ab responses to nucleic acid-containing Ags.

Figure 1. Model for T-bet induction in B cells and its role in B cell fate

Synergistic signaling via B cell antigen receptor (BCR), Toll-like receptor 7 (TLR7), and IFNγR in B cells leads to the induction of high levels of T-bet expression, which in turn drive the expression of an ABC phenotype and class switching to the production of IgG2a antibodies.

Figure 2. ABCs in age, autoimmunity and infection

Function and the outcome of ABCs appearance in aged animals is still unknown. In autoimmune animals, ABCs produce high titers of autoantibodies (mostly of IgG2a/c isotype) upon stimulation, which may be the cause of autoimmunity. During the infection, ABCs produce anti-viral IgG (mostly IgG2a/c), which is required for the efficient viral clearance.