Memory B cell differentiation from germinal centers

Establishment of humoral immune memory depends on two layers of defense: pre-existing antibodies secreted by long-lived plasma cells; and the antibodies produced by antigen-reactivated memory B cells. Memory B cells can now be considered as a second layer of defense upon re-infection by variant pathogens that have not been cleared by the long-lived plasma cell-mediated defense. Affinity-matured memory B cells are derived from the germinal center (GC) reaction, but the selection mechanism of GC B cells into the memory compartment is still incompletely understood. Recent studies have revealed the critical determinants of cellular and molecular factors for memory B cell differentiation from the GC reaction. In addition, the contribution of antibody-mediated feedback regulation to B cell selection, as exemplified by the B cell response upon COVID-19 mRNA vaccination, has now garnered considerable attention, which may provide valuable implications for future vaccine design.