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 ...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.展开更多
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)+2 种基金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.
文摘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.
