Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2

  1. Sandra C. A. Nielsen
  2. Fan Yang
  3. Katherine J. L. Jackson
  4. Ramona A. Hoh
  5. Katharina Röltgen
  6. Bryan Stevens
  7. Ji-Yeun Lee
  8. Arjun Rustagi
  9. Angela J. Rogers
  10. Abigail E. Powell
  11. Javaria Najeeb
  12. Ana R. Otrelo-Cardoso
  13. Kathryn E. Yost
  14. Bence Daniel
  15. Howard Y. Chang
  16. Ansuman T. Satpathy
  17. Theodore S. Jardetzky
  18. Peter S. Kim
  19. Taia T. Wang
  20. Benjamin A. Pinsky
  21. Catherine A. Blish
  22. Scott D. Boyd

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Abstract

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the 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 extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve 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 other zoonotic spillover coronaviruses.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.08.194456: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationFour randomized bases were included upstream of the barcodes on the IGHJ primer (gDNA libraries) and constant region primer (isotype libraries) for Illumina clustering.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    An enzyme-linked immunosorbent assay (ELISA) based on a protocol described in (Stadlbauer et al., 2020) was performed to detect anti-SARS-CoV and anti-SARS-CoV-2 spike RBD antibodies in plasma samples from COVID-19 patients.
    anti-SARS-CoV
    suggested: None
    anti-SARS-CoV-2 spike RBD
    suggested: None
    After blocking plates with 3% non-fat milk in PBS containing 0.1% Tween 20, plasma samples were incubated at a dilution of 1:100 and bound antibodies were detected with goat anti-human IgM/HRP (Sigma: cat.
    anti-human IgM/HRP
    suggested: None
    ELISA testing of mAbs: ELISA conditions for mAbs were as described for COVID-19 plasma samples with the following modifications: two-fold serial dilutions of mAbs were tested, starting at 100 μg/mL for intra-COVID-19 convergent antibodies or peanut-specific negative mAb controls, or at 0.506 μg/mL for mAb CR3022; plates were coated overnight with RBD (0.1 μg per well), S1 (0.1 μg per well), or spike protein (0.3 μg per well); and bound mAbs were detected with rabbit anti-human IgG gamma chain-specific/HRP (Agilent: cat.
    anti-human IgG gamma chain-specific/HRP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    mAb expression and purification: Constructs were transiently transfected in HEK293-EBNA1-6E cells (NRC) at a density of 1.2-1.6 million cells/mL using 25 kDa linear polyethylenimine (PEI) at a 3:1 PEI:DNA ratio in OptiMEM reduced serum medium (Gibco), with a heavy chain: light chain ratio of 1:1.
    HEK293-EBNA1-6E
    suggested: RRID:CVCL_HF20)
    Software and Algorithms
    SentencesResources
    The V, D, and J gene segments and V-D (N1), and D-J (N2) junctions were identified using the IgBLAST alignment program (Ye et al., 2013).
    IgBLAST
    suggested: (IgBLAST, RRID:SCR_002873)
    Analyses were conducted in R (Team, 2017) using base packages for statistical analysis and the ggplot2 package for graphics (Wickham, 2016).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.07.08.194456 on bioRxiv