Strength in diversity: Phenotypic, functional, and molecular heterogeneity within the memory B cell repertoire.

ABSTRACT

The vast majority of vaccines exploit antibody memory to induce lasting immunity. Memory B cells are generated during the initial response to infection, but persist long after the infection has cleared. Immune memory success relies on its adaptability in response to different pathogens, variants of a single pathogen, and in balancing persistence with reactivation and plasma cell differentiation. This is likely achieved by producing a B cell memory population that is highly diverse, and recent work has highlighted the importance of memory B cell subsets in mediating the dichotomous roles of the population. This review will detail the characterization, function and both intrinsic and extrinsic regulation of different memory B cell subsets memory B cell precursors within the germinal center, phenotypic, and functional heterogeneity of the memory B cell population, and memory B cell subsets that reside in tissues. In particular, understanding the genetic and epigenetic regulation of memory B diversity may be critical for gaining insight into B cell memory responses to pathogens that have evaded effective vaccine design. Therefore, there is a vital need to understand the mechanisms underlying the origin, function and translational potential of the heterogeneity within the memory B cell population.