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