CD62L expression marks SARS-CoV-2 memory B cell subset with preference for neutralizing epitopes

Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (Bmem) cells have variation in the neutralizing activities. Here, by combining single Bmem cell profiling with antibody functional assessment, we dissected the phenotype of Bmem cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals. The neutralizing subset was marked by an elevated CD62L expression and characterized by distinct epitope preference and usage of convergent VH (variable region of immunoglobulin heavy chain) genes, accounting for the neutralizing activities. Concordantly, the correlation was observed between neutralizing antibody titers in blood and CD62L+ subset, despite the equivalent RBD binding of CD62L+ and CD62L- subset. Furthermore, the kinetics of CD62L+ subset differed between the patients who recovered from different COVID-19 severities. Our Bmem cell profiling reveals the unique phenotype of Bmem cell subset that harbors potently neutralizing BCRs, advancing our understanding of humoral protection.

Automated summary

By analyzing single Bmem cells and assessing antibody function, we have identified the characteristics of Bmem cells that carry potent neutralizing antibodies in COVID-19 convalescent individuals. These neutralizing antibodies are marked by elevated CD62L expression, distinct epitope preference, and usage of convergent VH genes, which contribute to their neutralizing activities. Despite equivalent receptor binding, there is a correlation between neutralizing antibody titers and the CD62L+ subset. Moreover, the dynamics of the CD62L+ subset differ among patients with varying COVID-19 severities. Our Bmem cell profiling reveals the unique phenotype of the subset harboring potent neutralizing BCRs and enhances our understanding of humoral protection.