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.

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 CD45RB^lo 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 CD45RB^lo memory B cells. Moreover, in both COVID-19 patients and mRNA vaccination, CD45RB^lo 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 CD45RB^lo memory B cells contribute to SARS-CoV-2 infection and vaccination. Activated memory B cells express a variety of markers. Here, by mass cytometry and CITE-seq, the authors identify differential expression of CD45RB as a marker distinguishing classical and atypical/non-classical memory B cells, with the former being more prominent during sepsis, while the latter being more abundant in COVID-19 infection or vaccination. [ABSTRACT FROM AUTHOR]