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.