Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France; Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France.
Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France; Inovarion, Paris, France.
Cell. 2021 Mar 4;184(5):1201-1213.e14. doi: 10.1016/j.cell.2021.01.050. Epub 2021 Feb 2.
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 细胞在宿主抵抗病毒方面发挥着重要作用,但迄今为止,它们在 SARS-CoV-2 背景下的作用仍未得到充分证实。我们在此报告了一项对轻度和重度 COVID-19 患者长达 6 个月的 B 细胞反应的纵向单细胞和库特征分析。独特的 SARS-CoV-2 刺突特异性激活 B 细胞克隆推动了早期抗体分泌细胞爆发以及持久的同步生发中心反应。虽然包括先前存在的交叉反应季节性β冠状病毒特异性克隆在内的高度突变的记忆 B 细胞在反应早期被招募,但中和 SARS-CoV-2 RBD 特异性克隆随时间积累,并在很大程度上促成了晚期、显著稳定的记忆 B 细胞库。这些细胞显示出其可变区基因中的体细胞突变随时间的推移而明显积累,突出了生发中心的成熟。总的来说,这些发现表明抗原驱动的激活持续存在,并在 SARS-CoV-2 感染后长达 6 个月成熟,可能提供长期保护。