GSE175427
Limited access to antigen drives the generation of early B cell memory while restraining the plasmablast response
The cell fate decisions between plasmablasts (PBs), germinal center B cells (GCBCs) and non-GC-derived memory B cells (MBCs) during early B cell activation determine the outcome of the immune responses to pathogens and vaccines. In this study, we dissected these poorly characterized lineage choices by single-cell RNA-sequencing. Early after immunization, a homogenous population of activated precursors (APs) gave rise to a transient wave of PBs, followed a day later by the emergence of the first GCBCs, with the transcriptomes of both rapidly diverging from that of APs. The majority of APs started to withdraw from the cell cycle very early on and gave rise to GC-independent MBCs, a developmental transition that involved limited transcriptional changes. These events were controlled by antigen availability, and provision of antigen excess interfered with cell cycle exit and induced a new wave of PBs. Fate mapping experiments revealed a prominent contribution of GC-independent memory to the overall MBC pool. Quiescent cells with an MBC phenotype also dominated the early response to immunization in primates, indicating evolutionary conservation. Thus, excess APs, kept in reserve as early MBCs, can be rapidly re-recruited if failure to contain a threat is manifested by increased antigen availability, thus providing a feedback mechanism for rapid readjustment of the immune response. Overall design: 16 bulk RNA-seq samples