Age-associated B cells: key mediators of both protective and autoreactive humoral responses

A subset of B cells with unique phenotypic and functional features-termed Age-associated B cells (ABCs)-has recently been identified in both mice and humans. These cells are characterized by a T-BET driven transcriptional program, robust responsiveness to TLR7 and TLR9 ligands, and a propensity for IgG2a/c production. Beyond their age-related accumulation, these cells play roles in both normal and pathogenic humoral immune responses regardless of host age. Thus, B cells with the ABC phenotype and transcriptional signature appear during viral, bacterial, and parasitic infections, but also arise during humoral autoimmune disease in both mouse models and humans. These observations suggest that both autoantigens and certain classes of pathogens provide the signals required for ABC differentiation. Herein, we review the discovery and features of ABCs, and propose that they are a memory subset generated by nucleic acid-containing antigens in the context of a promoting inflammatory cytokine milieu.