新冠病毒特异性FCRL3+FCGR2B+记忆B细胞亚群的鉴定及抗体功能的机制研究

新冠肺炎疫情在世界范围内快速暴发，目前尚无有效的治疗方法。迫切需要探索机体抗病毒的免疫机制及研发特异性防治药物。前期，本人利用单细胞测序技术获得了256个新冠病毒特异性记忆B细胞的转录组信息，表达纯化出其中234株新冠病毒特异性抗体，从单细胞转录组测序结果聚类分析中发现了高表达抑制性受体FCRL3和FCGR2B的B细胞亚群。在此基础上，本申请项目计划对新冠病毒特异性FCRL3+FCGR2B+记忆B细胞亚群进行鉴定，探索高表达抑制性受体的B细胞在新冠病毒类的急性病毒感染中对病毒的清除作用及对疾病发展进程和免疫再应答的影响，实现从免疫细胞层面上恢复B细胞功能，为新冠肺炎的救治提供新的思路；对234株抗体进行抗病毒能力的系统评估，获得高效抗病毒抗体，为临床上治疗新冠肺炎提供一种可选的方法；分析抗体中和活性、ADCC效应及转录组三者间的相关性，从单细胞层面上探索抗病毒抗体的产生和作用机制。

The outbreak of COVID-19 has spread rapidly around the world and there is no effective treatment available at present. Therefore, there is an urgent need to explore the mechanism of antiviral immunity and develop specific therapeutic drugs against SARS-CoV-2. In the previous study, I obtained the transcriptome information of 256 SARS-CoV-2 specific memory B cells by single-cell sequencing technology, and expressed and purified 234 SARS-CoV-2 specific antibodies. Cluster analysis of single-cell transcriptome sequencing results revealed a group of B cells highly expressing inhibitory receptors FCRL3 and FCGR2B. On this basis, this application project plans to identify SARS-CoV-2 specific FCRL3 + FCGR2B + memory B cell subsets, and explore the virus-clearing effect of B cells with high expression of inhibitory receptor in SARS-CoV-2-like acute virus infection , as well as the influence on disease progression and immune reresponse. Thus, the function of B cells can be restored at the level of immune cells, providing a new idea for the treatment of COVID-19. Systemic evaluation of the antiviral ability of 234 antibodies was carried out to obtain effective antiviral antibodies, providing an alternative method for the clinical treatment of COVID-19.The correlation between the neutralization activity of antibody, ADCC effect and transcriptome was analyzed to explore the production and action mechanism of antiviral antibody from the single-cell level.