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

作　　者：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 

机构地区：[1]School of Public Health(Shenzhen),Sun Yat-sen University,Shenzhen,China [2]Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,China [3]Pulmonary and critical care medicine,The Third Peopled Hospital of Dongguan City,Dongguan,Guangdong Province,China [4]Hangzhou ImmuQuad Biotechnologies,Hangzhou,China [5]Zhejiang-California International NanoSystems Institute,Zhejiang University,Hangzhou,China [6]lnfection and Immunity Center,School of Medicine,Sun Yat-sen University,Shenzhen,China [7]Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,School of Medicine,Sun Yat-sen University,Guangzhou,China [8]Guangdong Provincial Key Laboratory of Biomedical Imaging,The Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai,China [9]Department of Infectious Diseases,The Ninth Peopled Hospital of Dongguan City,Dongguan,Guangdong Province,China [10]Department of Infectious Diseases,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong Province,China [11]School of Data and Computer Science,Sun Yat-sen University,Guangzhou,China [12]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai,China [13]Shenzhen Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Shenzhen,China [14]Genome Analysis Laboratory of the Ministry of Agriculture,Shenzhen,China [15]Agricultural Genomics Institute at Shenzhen,Chinese Academy of Agricultural Sciences,Shenzhen,China [16]Key Laboratory of Tropical Disease Control(Sun Yat-sen University),Ministry of Education,Guangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第6期1833-1844,共12页信号转导与靶向治疗（英文）

基　　金：supported by National Natural Science Foundation of China(31970881)and(82041046)to Y.Q.C.;Shenzhen Science and Technology Program under Grant(JCYJ20190807154603596 and JCYJ20200109142438111);the National Key Research and Development Project(2020YFC0841700)to M.W.;the National Natural Science Foundation of China(32041002)to D.Y.G.;the Special Fund for COVID-19 Epidemic Prevention&Control of Zhuhai City of China granted to S.D.C.

摘　　要：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.

关 键 词：PATIENTS SPECIFICITY LINKING 

分 类 号：R563.1[医药卫生—呼吸系统]