Plasticity and Heterogeneity in the Generation of Memory B Cells and Long-Lived Plasma Cells: The Influence of Germinal Center Interactions and Dynamics

In the humoral response, short-lived plasmablasts generate an early burst of Ab that probably plays an initial protective role. Simultaneously, another arm of the response is often triggered that leads to delayed effector function but long-term protection. This arm comprises the germinal center response and its products: long-lived memory B (B(mem)) cells and plasma cells (PCs). The factors that control the differentiation of PCs and B(mem) cells, as well as the composition and function of the memory compartment--how it self-renews while generating rapid secondary effector function--are poorly understood. Recent work in mice and humans is beginning to illuminate these issues. We review this progress, with emphasis on events in the germinal center, especially B-T interactions, which influence the development of memory and PC compartments and on B(mem) cell heterogeneity that may underlie flexibility and self-renewal of long-lived humoral immunity.