Glaros V, Rauschmeier R, Artemov AV, Reinhardt A, Ols S, Emmanouilidi A, Gustafsson C, You Y, Mirabello C, Björklund ÅK, Perez L, King NP, Månsson R, Angeletti D, Loré K, Adameyko I, Busslinger M, Kreslavsky T
Immunity 54 (9) 2005-2023.e10 [2021-09-14; online 2021-09-16]
Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.