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.

记忆 B 细胞在宿主防御病毒中起着基础性作用，但迄今为止，它们在 SARS-CoV-2 背景下的作用相对不稳定。我们在这里报告了轻度和重度 COVID-19 患者长达 6 个月的 B 细胞反应的纵向单细胞和库分析。不同的 SARS-CoV-2 刺突特异性激活的 B 细胞克隆促进了早期抗体分泌细胞的爆发以及持久的同步生发中心反应。虽然高度突变的记忆 B 细胞，包括预先存在的交叉反应性季节性 Betacoronavirus 特异性克隆，在反应早期被招募，中和了随时间积累的 SARS-CoV-2 RBD 特异性克隆，并在很大程度上促成了晚期，非常稳定，记忆 B 细胞池。突出生发中心成熟，随着时间的推移，这些细胞在其可变区基因中显示出明显的体细胞突变积累。总体而言，这些发现表明，抗原驱动的激活在 SARS-CoV-2 感染后持续存在并成熟长达 6 个月，并可能提供长期保护。