Basics of memory B‐cell responses: lessons from and for the real world

The production of pathogen‐specific B cells and antibodies underlies protective immunity elicited by most vaccines and many infections. Humoral immunity follows a regulated process by which high‐affinity antibody‐secreting plasma cells and memory B cells are generated. Yet for certain pathogens, protective immunity is inefficiently generated and/or maintained. For example, Dengue virus infections lead to lasting immunity against re‐infection by the same serotype. However, if infected with a different Dengue serotype, the individual is predisposed to more severe disease than if he/she was completely naive. As another example, both natural infections with or vaccination against malaria do not necessarily lead to lasting immunity, as the same individual can be re‐infected many times over the course of a lifetime. In this review, we discuss how these real‐world problems can both instruct and be informed by recent basic studies using model organisms and antigens. An emphasis is placed on protective epitopes and functional distinctions between memory B‐cell subsets in both mice and humans. Using flavivirus and Plasmodium infections as examples, we also speculate on the differences between ineffective B‐cell responses that actually occur in the real world, and perfect‐world responses that would generate lasting immunity.