Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. Highaffinity cells are proposed to preferentially select into this compartment, potentiating the immune response. We used single -cell RNA-seq to track the germinal center (GC) development of Ighg2A10 B cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites, we identified 3 populations of cells in the GC light zone (LZ). One LZ population expressed a gene signature associated with the initiation of PC differentiation and readily formed PCs in vitro. The estimated affinity of these pre -PC B cells was indistinguishable from that of LZ cells that remained in the GC. This remained true when high- or low -avidity recombinant PfCSP proteins were used as immunogens. These findings suggest that the initiation of PC development occurs via an affinity -independent process.