Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response

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.

Automated summary

Cell fate decisions during early B cell activation dictate the immune response to pathogens and vaccines. The study found that a homogeneous population of activated precursors gives rise to plasmablasts and germinal center B cells after antigen exposure, with most precursors quickly exiting the cell cycle to form early memory B cells. The decline in antigen availability controls these events, demonstrating the plasticity of the immune response.