Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19 2886

Abstract Description Resting memory B cells can be divided into classical or atypical groups, but the heterogenous marker expression on activated memory B cells makes similar classification difficult. Here, by longitudinal analysis of mass cytometry and CITE-seq data from cohorts with COVID-19, bacterial sepsis, or BNT162b2 mRNA vaccine, we observe that resting B cell memory consist of classical CD45RB+ memory and CD45RBlo memory, of which the latter contains of two distinct groups of CD11c+ atypical and CD23+ non-classical memory cells. CD45RB levels remain stable in these cells after activation, thereby enabling the tracking of activated B cells and plasmablasts derived from either CD45RB+ or CD45RBlo memory B cells. Moreover, in both COVID-19 patients and mRNA vaccination, CD45RBlo B cells formed the majority of SARS-CoV2 specific memory B cells and correlated with serum antibodies, while CD45RB+ memory are activated by bacterial sepsis. Our results thus identify that stably expressed CD45RB levels can be exploited to trace resting memory B cells and their activated progeny, and suggest that atypical and non-classical CD45RBlo memory B cells contribute to SARS-CoV-2 infection and vaccination. Funding Sources Takeda Science Foundation “2021 High-Risk Emerging Infectious Disease Research Grant”, AMED under Grant Number JP223fa627002, Nippon Foundation FY2022 CiDER Cross-Departmental “Infectious Diseases” Research Promotion Program, “The Nippon Foundation - Osaka University Project for Infectious Disease Prevention” Topic Categories Immune Mechanisms of Human Disease (HUM)