Different B cell subpopulations show distinct patterns in their IgH repertoire metrics

  1. Marie Ghraichy
  2. Valentin von Niederhäusern
  3. Aleksandr Kovaltsuk
  4. Jacob D Galson
  5. Charlotte M Deane
  6. Johannes Trück  Is a corresponding author
  1. University Children's Hospital, University of Zurich (UZH), Switzerland
  2. University of Oxford, United Kingdom
  3. Alchemab Ltd, United Kingdom

Abstract

Several human B-cell subpopulations are recognized in the peripheral blood, which play distinct roles in the humoral immune response. These cells undergo developmental and maturational changes involving VDJ recombination, somatic hypermutation and class switch recombination, altogether shaping their immunoglobulin heavy chain (IgH) repertoire. Here, we sequenced the IgH repertoire of naïve, marginal zone, switched and plasma cells from 10 healthy adults along with matched unsorted and in silico separated CD19+ bulk B cells. Using advanced bioinformatic analysis and machine learning, we show that sorted B cell subpopulations are characterised by distinct repertoire characteristics on both the individual sequence and the repertoire level. Sorted subpopulations shared similar repertoire characteristics with their corresponding in silico separated subsets. Furthermore, certain IgH repertoire characteristics correlated with the position of the constant region on the IgH locus. Overall, this study provides unprecedented insight over mechanisms of B cell repertoire control in peripherally circulating B cell subpopulations.

Data availability

Raw data used in this study are available at the NCBI Sequencing Read Archive (www.ncbi.nlm.nih.gov/sra) under BioProject number PRJNA748239 including metadata meeting MiAIRR standards (32). The processed dataset is available in Zenodo (https://doi.org/10.5281/zenodo.3585046) along with the protocol describing the exact processing steps with the software tools and version numbers.

The following data sets were generated

Article and author information

Author details

  1. Marie Ghraichy

    University Children's Hospital, University of Zurich (UZH), Zurich, Switzerland
    Competing interests
    No competing interests declared.
  2. Valentin von Niederhäusern

    University Children's Hospital, University of Zurich (UZH), Zurich, Switzerland
    Competing interests
    No competing interests declared.
  3. Aleksandr Kovaltsuk

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Jacob D Galson

    NA, Alchemab Ltd, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4916-800X
  5. Charlotte M Deane

    University of Oxford, Oxford, United Kingdom
    Competing interests
    Charlotte M Deane, Reviewing editor, eLife.
  6. Johannes Trück

    University Children's Hospital, University of Zurich (UZH), Zurich, Switzerland
    For correspondence
    Johannes.Trueck@kispi.uzh.ch
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0418-7381

Funding

Swiss National Science Foundation (PZ00P3_161147)

  • Johannes Trück

Swiss National Science Foundation (PZ00P3_183777)

  • Johannes Trück

Gottfried und Julia Bangerter-Rhyner-Stiftung

  • Johannes Trück

Olga Mayenfisch Stiftung

  • Johannes Trück

Palatin-Stiftung

  • Johannes Trück

Biotechnology and Biological Sciences Research Council (BB/M011224/1)

  • Aleksandr Kovaltsuk

UCB Pharma Ltd

  • Aleksandr Kovaltsuk

Royal Commission for the Exhibition of 1851 Industrial Fellowship

  • Aleksandr Kovaltsuk

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Buffy coat samples were obtained from 10 anonymous healthy adults, hence no approval from the local ethics committee was necessary.

Reviewing Editor

  1. Tomohiro Kurosaki, Osaka University, Japan

Version history

  1. Received: August 17, 2021
  2. Preprint posted: September 5, 2021 (view preprint)
  3. Accepted: October 17, 2021
  4. Accepted Manuscript published: October 18, 2021 (version 1)
  5. Version of Record published: November 1, 2021 (version 2)

Copyright

© 2021, Ghraichy et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marie Ghraichy
  2. Valentin von Niederhäusern
  3. Aleksandr Kovaltsuk
  4. Jacob D Galson
  5. Charlotte M Deane
  6. Johannes Trück
(2021)
Different B cell subpopulations show distinct patterns in their IgH repertoire metrics
eLife 10:e73111.
https://doi.org/10.7554/eLife.73111

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