Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19

Zachary Montague; Huibin Lv; Jakub Otwinowski; William S DeWitt; Giulio Isacchini; Garrick K Yip; Wilson W Ng; Owen Tak-Yin Tsang; Meng Yuan; Hejun Liu; Ian A Wilson; J S Malik Peiris; Nicholas C Wu; Armita Nourmohammad; Chris Ka Pun Mok

doi:10.1016/j.celrep.2021.109173

Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19

Cell Rep. 2021 May 25;35(8):109173. doi: 10.1016/j.celrep.2021.109173. Epub 2021 May 9.

Authors

Affiliations

¹ Department of Physics, University of Washington, 3910 15th Ave. Northeast, Seattle, WA 98195, USA.
² HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
³ Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany.
⁴ Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, WA 98195, USA; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.
⁵ Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany; Laboratoire de physique de l'ecole normale supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, 75005 Paris, France.
⁶ Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong SAR, China.
⁷ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁸ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁹ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: [email protected].
¹⁰ Department of Physics, University of Washington, 3910 15th Ave. Northeast, Seattle, WA 98195, USA; Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany; Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA. Electronic address: [email protected].
¹¹ HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: [email protected].

Abstract

Individuals with the 2019 coronavirus disease (COVID-19) show varying severity of the disease, ranging from asymptomatic to requiring intensive care. Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, we still lack an understanding of the overall landscape of B cell receptor (BCR) repertoires in individuals with COVID-19. We use high-throughput sequencing of bulk and plasma B cells collected at multiple time points during infection to characterize signatures of the B cell response to SARS-CoV-2 in 19 individuals. Using principled statistical approaches, we associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among individuals as candidates for responses specific to SARS-CoV-2. Using single-cell sequencing, we verify the reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identify the natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in some individuals. Our results provide insights important for development of rational therapies and vaccines against COVID-19.

Keywords: B cell clonal expansion; B cell repertoires; BCR selection; BCR sharing; COVID-19; SARS-CoV-2; antibody; cross-reactivity.

MeSH terms

Animals
Antibodies, Viral / immunology
B-Lymphocytes / immunology*
COVID-19 / genetics
COVID-19 / immunology*
Cross Reactions*
Epitopes
High-Throughput Nucleotide Sequencing
Humans
Receptors, Antigen, B-Cell / genetics*
Receptors, Antigen, B-Cell / immunology*
SARS-CoV-2 / immunology*
Severity of Illness Index
Sf9 Cells
Single-Cell Analysis
Spike Glycoprotein, Coronavirus / immunology

Substances

Antibodies, Viral
Epitopes
Receptors, Antigen, B-Cell
Spike Glycoprotein, Coronavirus

Abstract

MeSH terms

Substances

Grants and funding