An antigen to remember: regulation of B cell memory in health and disease

•IgM+ MBCs are early responders in malaria and may be vital in parasite clearance.•MBC heterogeneity may be expanded to tackle varying antigen in chronic infection.•Atypical MBCs, CD21neg and T-bet+CD11c+ B cells may share transcriptional programs.•In vivo studies will allow insight into intrinsic and extrinsic regulators of MBCs.

Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM+ MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown. Similarly, the T-bet-driven transcriptional program drives formation of MBCs phenotypically similar to atypical MBCs. Identifying protective or detrimental roles of MBC subsets, and their regulators, will be important for clinical intervention.