Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2

Sandra C A Nielsen; Fan Yang; Katherine J L Jackson; Ramona A Hoh; Katharina Röltgen; Grace H Jean; Bryan A Stevens; Ji-Yeun Lee; Arjun Rustagi; Angela J Rogers; Abigail E Powell; Molly Hunter; Javaria Najeeb; Ana R Otrelo-Cardoso; Kathryn E Yost; Bence Daniel; Kari C Nadeau; Howard Y Chang; Ansuman T Satpathy; Theodore S Jardetzky; Peter S Kim; Taia T Wang; Benjamin A Pinsky; Catherine A Blish; Scott D Boyd

doi:10.1016/j.chom.2020.09.002

Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2

Cell Host Microbe. 2020 Oct 7;28(4):516-525.e5. doi: 10.1016/j.chom.2020.09.002. Epub 2020 Sep 3.

Authors

Sandra C A Nielsen¹, Fan Yang¹, Katherine J L Jackson², Ramona A Hoh¹, Katharina Röltgen¹, Grace H Jean³, Bryan A Stevens¹, Ji-Yeun Lee¹, Arjun Rustagi⁴, Angela J Rogers⁵, Abigail E Powell⁶, Molly Hunter⁷, Javaria Najeeb⁸, Ana R Otrelo-Cardoso⁸, Kathryn E Yost⁹, Bence Daniel¹, Kari C Nadeau¹⁰, Howard Y Chang¹¹, Ansuman T Satpathy¹, Theodore S Jardetzky¹², Peter S Kim¹³, Taia T Wang¹⁴, Benjamin A Pinsky¹, Catherine A Blish¹⁵, Scott D Boyd¹⁶

Affiliations

¹ Department of Pathology, Stanford University, Stanford, CA 94305, USA.
² Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
³ Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA.
⁶ Stanford ChEM-H and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
⁷ ATUM, Newark, CA, 94560, USA.
⁸ Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
⁹ Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
¹⁰ 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.
¹¹ Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
¹² 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.
¹³ Stanford ChEM-H and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
¹⁴ 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.
¹⁵ 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.
¹⁶ 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.

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.

Keywords: B cells; COVID-19; SARS-CoV-2; antibodies; antibody repertoire; clonal expansion; convergent antibody response; immunogenetics; immunology; primary infection.

MeSH terms

Adult
Aged
Aged, 80 and over
Antibodies, Viral / blood
Antibodies, Viral / genetics
Antibodies, Viral / immunology*
Antibody Formation
B-Lymphocytes / immunology*
Betacoronavirus / genetics
Betacoronavirus / immunology*
COVID-19
Coronavirus Infections / immunology*
Coronavirus Infections / virology*
Female
HEK293 Cells
Humans
Immunogenetics
Immunoglobulin A / genetics
Immunoglobulin A / immunology
Immunoglobulin G / genetics
Immunoglobulin G / immunology
Male
Middle Aged
Pandemics
Pneumonia, Viral / immunology*
Pneumonia, Viral / virology*
SARS-CoV-2
Sequence Analysis
Spike Glycoprotein, Coronavirus / immunology

Substances

Antibodies, Viral
Immunoglobulin A
Immunoglobulin G
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

MeSH terms

Substances

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