Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq

He, Bing; Liu, Shuning; Wang, Yuanyuan; Xu, Mengxin; Cai, Wei; Liu, Jia; Bai, Wendi; Ye, Shupei; Ma, Yong; Hu, Hengrui; Meng, Huicui; Sun, Tao; Li, Yanling; Luo, Huanle; Shi, Mang; Du, Xiangjun; Zhao, Wenjing; Chen, Shoudeng; Yang, Jingyi; Zhu, Haipeng; Jie, Yusheng; Yang, Yuedong; Guo, Deyin; Wang, Qiao; Liu, Yuwen; Yan, Huimin; Wang, Manli; Chen, Yao-Qing

B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11c(high) CD95(high)) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.