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

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 (B _mem ) cells have variation in the neutralizing activities. Here, by combining single B _mem cell profiling with antibody functional assessment, we dissected the phenotype of B _mem 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 V _H (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 B _mem cell profiling reveals the unique phenotype of B _mem cell subset that harbors potently neutralizing BCRs, advancing our understanding of humoral protection.