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Analysis of B Cell Receptor Repertoires Reveals Key Signatures of the Systemic B Cell Response after SARS-CoV-2 Infection.
Zhang, Yudi; Yan, Qihong; Luo, Kun; He, Ping; Hou, Ruitian; Zhao, Xinwei; Wang, Qian; Yi, Haisu; Liang, Huan; Deng, Yijun; Hu, Fengyu; Li, Feng; Liu, Xinglong; Feng, Ying; Li, Pingchao; Qu, Linbing; Chen, Zhaoming; Pan-Hammarström, Qiang; Feng, Liqiang; Niu, Xuefeng; Chen, Ling.
  • Zhang Y; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Yan Q; University of Chinese Academy of Science, Beijing, China.
  • Luo K; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • He P; University of Chinese Academy of Science, Beijing, China.
  • Hou R; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Zhao X; University of Chinese Academy of Science, Beijing, China.
  • Wang Q; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Yi H; University of Chinese Academy of Science, Beijing, China.
  • Liang H; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Deng Y; University of Chinese Academy of Science, Beijing, China.
  • Hu F; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Li F; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Liu X; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Feng Y; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Li P; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Qu L; Guangzhou Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • Chen Z; Guangzhou Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • Pan-Hammarström Q; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Feng L; University of Chinese Academy of Science, Beijing, China.
  • Niu X; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
  • Chen L; Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.
J Virol ; 96(4): e0160021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1759291
ABSTRACT
A comprehensive study of the B cell response against SARS-CoV-2 could be significant for understanding the immune response and developing therapeutical antibodies and vaccines. To define the dynamics and characteristics of the antibody repertoire following SARS-CoV-2 infection, we analyzed the mRNA transcripts of immunoglobulin heavy chain (IgH) repertoires of 24 peripheral blood samples collected between 3 and 111 days after symptom onset from 10 COVID-19 patients. Massive clonal expansion of naive B cells with limited somatic hypermutation (SHM) was observed in the second week after symptom onset. The proportion of low-SHM IgG clones strongly correlated with spike-specific IgG antibody titers, highlighting the significant activation of naive B cells in response to a novel virus infection. The antibody isotype switching landscape showed a transient IgA surge in the first week after symptom onset, followed by a sustained IgG elevation that lasted for at least 3 months. SARS-CoV-2 infection elicited poly-germ line reactive antibody responses. Interestingly, 17 different IGHV germ line genes recombined with IGHJ6 showed significant clonal expansion. By comparing the IgH repertoires that we sequenced with the 774 reported SARS-CoV-2-reactive monoclonal antibodies (MAbs), 13 shared spike-specific IgH clusters were found. These shared spike-specific IgH clusters are derived from the same lineage of several recently published neutralizing MAbs, including CC12.1, CC12.3, C102, REGN10977, and 4A8. Furthermore, identical spike-specific IgH sequences were found in different COVID-19 patients, suggesting a highly convergent antibody response to SARS-CoV-2. Our analysis based on sequencing antibody repertoires from different individuals revealed key signatures of the systemic B cell response induced by SARS-CoV-2 infection. IMPORTANCE Although the canonical delineation of serum antibody responses following SARS-CoV-2 infection has been well established, the dynamics of antibody repertoire at the mRNA transcriptional level has not been well understood, especially the correlation between serum antibody titers and the antibody mRNA transcripts. In this study, we analyzed the IgH transcripts and characterized the B cell clonal expansion and differentiation, isotype switching, and somatic hypermutation in COVID-19 patients. This study provided insights at the repertoire level for the B cell response after SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / B-Lymphocytes / Receptors, Antigen, B-Cell / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Vaccines Limits: Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01600-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / B-Lymphocytes / Receptors, Antigen, B-Cell / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Vaccines Limits: Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01600-21