Signal Transduction and Targeted Therapy (May 2021)

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

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

DOI
https://doi.org/10.1038/s41392-021-00610-7
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 12

Abstract

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Abstract 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.