SARS-CoV-2 RBD-specific atypical memory B cells exhibit effector memory-like features in multi-dose mRNA vaccination

Abstract Memory B cell is a heterogenous population and such heterogeneity focus of active investigation. How distinct subsets memory cells respond to repeated novel antigen challenges as SARS-CoV-2 in human remains subject vigorous research. We employed fluorochrome-conjugated streptavidin tetramers bound with RBD wild-type omicron variant (B.1.1.529), respectively, sort RBD-specific performed CITE-seq investigate detailed dynamics transcriptomes, surface phenotyes clonality healthy mRNA vaccination cohort. PBMC samples 8 BNT162b2 vaccine recipients from 7 consecutive timepoints, before after each dose 3-times vaccination, were analyzed. found pulsating, yet increasing trend, frequency atypical among tetramer-binding vaccine. SCENIC analysis find subset-specific regulatory gene networks revealed have regulons genes related activation receptor clustering, signaling calcium-dependent compared classical only one shared clone between cells, suggesting infrequent interconversion the two subsets. Furthermore, in-vitro polyclonal stimulation showed higher antibody-secreting (ASC) pre-plasmablasts flow cytometry ASCs IgG ELISPOT assay, cells. These findings highlight effector memory-like features viral challenge potential target future design.