biostudies-literatureSutton HJNational Institute of Allergy and Infectious DiseasesIntramural NIH HHSNational Health and Medical Research CouncilNational Institutes of HealthDivision of Intramural Research245-255.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922795biostudies-literatureUnknown57(2)Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. High-affinity 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 Igh^g2A10 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.ImmunityLack of affinity signature for germinal center cells that have initiated plasma cell differentiation.PMC10922795GNT2003035GNT1158404ZIA AI001260GNT2008648Kelly HGParker BJTan JNeeman TGao XSutton HJLofgren MDacon CChatterjee DSeder RAIdris AHCockburn IAfalseLack 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. High-affinity 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 Igh^g2A10 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.2024-01-01T00:00:00Z2024 Feb2025-04-04T02:01:03.603Z2025-04-04T02:01:03.603ZS-EPMC109227953822815010.1016/j.immuni.2023.12.010