Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Sokal, Aurélien; Chappert, Pascal; Barba-Spaeth, Giovanna; Roeser, Anais; Fourati, Slim; Azzaoui, Imane; Vandenberghe, Alexis; Fernandez, Ignacio; Meola, Annalisa; Bouvier-Alias, Magali; Crickx, Etienne; Beldi-Ferchiou, Asma; Hue, Sophie; Languille, Laetitia; Michel, Marc; Baloul, Samia; Noizat-Pirenne, France; Luka, Marine; Mégret, Jérôme; Ménager, Mickaël; Pawlotsky, Jean-Michel; Fillatreau, Simon; Rey, Felix A.; Weill, Jean-Claude; Reynaud, Claude-Agnès; Mahévas, Matthieu

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.