Abstract

Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing. By comparing transcriptomes of B cells at different stages of differentiation from an in vitro model with ex vivo B cells and ASCs, we uncovered a novel pre-ASC population present ex vivo in lymphoid tissues. For the first time, a germinal-center-like population is identified in vitro from human naive B cells and possibly progresses into a memory B cell population through an alternative route of differentiation, thus recapitulating in vivo human GC reactions. Our work allows further detailed characterization of human B cell differentiation into ASCs or memory B cells in both healthy and diseased conditions.

Data availability

All raw fastq files and digital gene expression matrixes (DGE) are available at the Gene Expression Omnibus (GEO) repository under accession no. GSE214265.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Niels JM Verstegen

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5732-4979
  2. Sabrina Pollastro

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0950-7583
  3. Peter-Paul A Unger

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Casper Marsman

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. George Elias

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8419-9544
  6. Tineke Jorritsma

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Marij Streutker

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. kevin bassler

    Genomics and Immunoregulation, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4780-372X
  9. Kristian Haendler

    Genomics and Immunoregulation, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Theo Rispens

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Joachim L Schultze

    Genomics and Immunoregulation, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Anja ten Brinke

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Marc Beyer

    Genomics and Immunoregulation, University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Marieke SM van Ham

    Department of Immunopathology, Sanquin, Amsterdam, Netherlands
    For correspondence
    m.vanham@sanquin.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1999-9494

Funding

LSBR (1609)

  • Marieke SM van Ham

PPOC (17-34/ L2263)

  • Marieke SM van Ham

German research foundation (272482170)

  • Marc Beyer

German research foundation (SFB1454-432325352)

  • Marc Beyer

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

Ethics

Human subjects: All the healthy donors provided written informed consent following the protocol of the local institutional review board, the Medical Ethics Committee of Sanquin Blood Supply, and conforms to the principles of the Declaration of Helsinki.

Copyright

© 2023, Verstegen 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. Niels JM Verstegen
  2. Sabrina Pollastro
  3. Peter-Paul A Unger
  4. Casper Marsman
  5. George Elias
  6. Tineke Jorritsma
  7. Marij Streutker
  8. kevin bassler
  9. Kristian Haendler
  10. Theo Rispens
  11. Joachim L Schultze
  12. Anja ten Brinke
  13. Marc Beyer
  14. Marieke SM van Ham
(2023)
Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates
eLife 12:e83578.
https://doi.org/10.7554/eLife.83578

Share this article

https://doi.org/10.7554/eLife.83578

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