期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00610-7
关键词
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资金
- National Natural Science Foundation of China [31970881, 82041046, 32041002]
- Shenzhen Science and Technology Program [JCYJ20190807154603596, JCYJ20200109142438111]
- National Key Research and Development Project [2020YFC0841700]
- Special Fund for COVID-19 Epidemic Prevention AMP
- Control of Zhuhai City of China
This study revealed the frequency, diversity, and specificity of antibody immune responses following SARS-CoV-2 infection using the LIBRA-seq technology. The results showed that a specific memory B cell subgroup in convalescent COVID-19 patients had a higher proportion of SARS-CoV-2 antigen-labeled cells, and public antibody clonotypes were shared by distinct individuals. Additionally, antibodies isolated by LIBRA-seq exhibited high binding affinity and neutralizing activities against SARS-CoV-2.
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.
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