College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518103, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Hum Immunol. 2022 Feb;83(2):119-129. doi: 10.1016/j.humimm.2021.10.007. Epub 2021 Nov 4.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引发了 2019 年冠状病毒病(COVID-19)大流行。人们投入了巨大的国际努力来开发预防性疫苗和中和抗体。然而,人们对 SARS-CoV-2 病毒引起的 B 细胞免疫反应的了解仍然有限。在这里,我们报告了对 COVID-19 患者免疫球蛋白重链(IGH)库动态的全面描述。通过使用下一代测序技术,我们检测了患者免疫状态随时间的变化,并在 COVID-19 症状出现后发现了患者免疫系统中 IGH 的剧烈变化。尽管不同的患者对 SARS-CoV-2 感染有不同的免疫反应,但通过克隆型重叠、谱系扩增和克隆型网络分析,我们观察到在发病后 2-3 周,B 细胞克隆的克隆型重叠更高,并且存在大量的谱系扩增,这对 B 细胞免疫反应非常重要。同时,在 SARS-CoV-2 感染期间,IGHV3-74 和 IGHV4-34,以及 COVID-19 患者中的 IGHV4-39 对 V 基因使用的偏好比健康对照更丰富。总的来说,我们为 SARS-CoV-2 提供了一个免疫学资源,这将促进治疗开发和机制研究。