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Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2.
Cell Host Microbe. 2020 10 07; 28(4):516-525.e5.CH

Abstract

B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV.

Links

Publisher Full Text
ncbi.nlm.nih.gov
linkinghub.elsevier.com
PMC Free PDF

Authors+Show Affiliations

Nielsen SCA
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Yang F
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Jackson KJL
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Hoh RA
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Röltgen K
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Jean GH
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Stevens BA
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Lee JY
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Rustagi A
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
Rogers AJ
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.
Powell AE
Stanford ChEM-H and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Hunter M
ATUM, Newark, CA, 94560, USA.
Najeeb J
Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
Otrelo-Cardoso AR
Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
Yost KE
Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Daniel B
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Nadeau KC
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Chang HY
Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Satpathy AT
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Jardetzky TS
Department of Structural Biology, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Kim PS
Stanford ChEM-H and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Wang TT
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Pinsky BA
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Blish CA
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: cblish@stanford.edu.
Boyd SD
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, 94305, USA. Electronic address: sboyd1@stanford.edu.

MeSH

AdultAgedAged, 80 and overAntibodies, ViralAntibody FormationB-LymphocytesBetacoronavirusCOVID-19Coronavirus InfectionsFemaleHEK293 CellsHumansImmunogeneticsImmunoglobulin AImmunoglobulin GMaleMiddle AgedPandemicsPneumonia, ViralSARS-CoV-2Sequence AnalysisSpike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32941787

Citation

Nielsen, Sandra C A., et al. "Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2." Cell Host & Microbe, vol. 28, no. 4, 2020, pp. 516-525.e5.
Nielsen SCA, Yang F, Jackson KJL, et al. Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2. Cell Host Microbe. 2020;28(4):516-525.e5.
Nielsen, S. C. A., Yang, F., Jackson, K. J. L., Hoh, R. A., Röltgen, K., Jean, G. H., Stevens, B. A., Lee, J. Y., Rustagi, A., Rogers, A. J., Powell, A. E., Hunter, M., Najeeb, J., Otrelo-Cardoso, A. R., Yost, K. E., Daniel, B., Nadeau, K. C., Chang, H. Y., Satpathy, A. T., ... Boyd, S. D. (2020). Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2. Cell Host & Microbe, 28(4), 516-e5. https://doi.org/10.1016/j.chom.2020.09.002
Nielsen SCA, et al. Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2. Cell Host Microbe. 2020 10 7;28(4):516-525.e5. PubMed PMID: 32941787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2. AU - Nielsen,Sandra C A, AU - Yang,Fan, AU - Jackson,Katherine J L, AU - Hoh,Ramona A, AU - Röltgen,Katharina, AU - Jean,Grace H, AU - Stevens,Bryan A, AU - Lee,Ji-Yeun, AU - Rustagi,Arjun, AU - Rogers,Angela J, AU - Powell,Abigail E, AU - Hunter,Molly, AU - Najeeb,Javaria, AU - Otrelo-Cardoso,Ana R, AU - Yost,Kathryn E, AU - Daniel,Bence, AU - Nadeau,Kari C, AU - Chang,Howard Y, AU - Satpathy,Ansuman T, AU - Jardetzky,Theodore S, AU - Kim,Peter S, AU - Wang,Taia T, AU - Pinsky,Benjamin A, AU - Blish,Catherine A, AU - Boyd,Scott D, Y1 - 2020/09/03/ PY - 2020/07/08/received PY - 2020/08/13/revised PY - 2020/08/27/accepted PY - 2020/9/18/pubmed PY - 2020/10/27/medline PY - 2020/9/17/entrez KW - B cells KW - COVID-19 KW - SARS-CoV-2 KW - antibodies KW - antibody repertoire KW - clonal expansion KW - convergent antibody response KW - immunogenetics KW - immunology KW - primary infection SP - 516 EP - 525.e5 JF - Cell host & microbe JO - Cell Host Microbe VL - 28 IS - 4 N2 - B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/32941787/Human_B_Cell_Clonal_Expansion_and_Convergent_Antibody_Responses_to_SARS_CoV_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(20)30503-5 DB - PRIME DP - Unbound Medicine ER -