Memory B cell heterogeneity: Remembrance of things past

B cells that persist for long periods of time after antigen encounter exist as either antibody-producing plasma cells (long-lived plasma cells, LLPCs) that reside primarily in the bone marrow or rapidly responsive memory B cells (MBCs) that reside in the spleen and circulation. Although LLPCs are thought to be non-responsive to a secondary infection, MBCs respond to subsequent infection through the production of antibody-secreting cells, formation of new germinal centers (GCs), and repopulation of the memory pool. Dogma suggests that MBCs express class-switched, somatically hypermutated BCRs after undergoing a GC reaction. Yet this narrow view of MBCs has been challenged over the years and it is now well recognized that diverse MBC subsets exist in both rodents and humans. Here, we review current thoughts on the phenotypic and functional characteristics of MBCs, focusing on a population of somatically hypermutated, high affinity IgM⁺ MBCs that are rapidly responsive to a secondary malaria infection.