Plasmodium-specific atypical memory B cells are short-lived activated B cells

  1. Damian Pérez-Mazliah
  2. Peter J Gardner
  3. Edina Schweighoffer
  4. Sarah McLaughlin
  5. Caroline Hosking
  6. Irene Tumwine
  7. Randall S Davis
  8. Alexandre J Potocnik
  9. Victor LJ Tybulewicz
  10. Jean Langhorne  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. MRC National Institute for Medical Research, United Kingdom
  3. University of Alabama at Birmingham, United States
  4. University of Edinburgh, United Kingdom

Abstract

A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite, Plasmodium chabaudi. In combination with a mosquito-initiated P. chabaudi infection, we show that Plasmodium-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that Plasmodium-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response.

Data availability

RNAseq transcriptome data have been deposited in GEO under accession code GSE115155.

The following data sets were generated

Article and author information

Author details

  1. Damian Pérez-Mazliah

    Malaria Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2156-2585
  2. Peter J Gardner

    Parasitology, Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4940-2639
  3. Edina Schweighoffer

    Immune Cell Biology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Sarah McLaughlin

    Malaria Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Caroline Hosking

    Malaria Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Irene Tumwine

    Malaria Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Randall S Davis

    Department of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1906-8219
  8. Alexandre J Potocnik

    School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Victor LJ Tybulewicz

    Immune Cell Biology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2439-0798
  10. Jean Langhorne

    Malaria Immunology Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    Jean.Langhorne@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2257-9733

Funding

Medical Research Council (FC001101)

  • Jean Langhorne

Wellcome (FC001101)

  • Jean Langhorne

Cancer Research UK (FC001101)

  • Jean Langhorne

National Institutes of Health (AI110553)

  • Randall S Davis

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

Ethics

Animal experimentation: The study was carried out in accordance with the UK Animals (Scientific Procedures) Act 1986, Home Office license 80/2538 and 70/8326. Was approved by the MRC National Institute for Medical Research Ethical Committee, The Francis Crick Institute Ethical Committee, and further approved by the Home Office of the UK upon granting of the HO license.

Reviewing Editor

  1. Facundo D Batista, Ragon Institute of MGH, MIT and Harvard, United States

Version history

  1. Received: July 4, 2018
  2. Accepted: October 31, 2018
  3. Accepted Manuscript published: November 2, 2018 (version 1)
  4. Version of Record published: November 19, 2018 (version 2)

Copyright

© 2018, Pérez-Mazliah 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. Damian Pérez-Mazliah
  2. Peter J Gardner
  3. Edina Schweighoffer
  4. Sarah McLaughlin
  5. Caroline Hosking
  6. Irene Tumwine
  7. Randall S Davis
  8. Alexandre J Potocnik
  9. Victor LJ Tybulewicz
  10. Jean Langhorne
(2018)
Plasmodium-specific atypical memory B cells are short-lived activated B cells
eLife 7:e39800.
https://doi.org/10.7554/eLife.39800

Share this article

https://doi.org/10.7554/eLife.39800

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