1. Immunology and Inflammation
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Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies

  1. Juan Rivera-Correa
  2. Maria Sophia Mackroth
  3. Thomas Jacobs
  4. Julian Schulze zur Wiesch
  5. Thierry Rolling
  6. Ana Rodriguez  Is a corresponding author
  1. New York University School of Medicine, United States
  2. University Medical Center Hamburg-Eppendorf, Germany
  3. Bernhard Nocht Institute for Tropical Medicine, Germany
Research Article
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Cite this article as: eLife 2019;8:e48309 doi: 10.7554/eLife.48309

Abstract

Anemia is a common complication of malaria which is characterized by the loss of infected and uninfected erythrocytes. In mice malaria models, clearance of uninfected erythrocytes is promoted by autoimmune anti-phosphatidylserine (PS) antibodies produced by T-bet+B-cells, which bind to exposed PS in erythrocytes, but the mechanism in patients is still unclear. In P. falciparum patients with anemia, we show that atypical memory FcRL5+T-bet+B-cells are expanded and associate with higher levels of anti-PS antibodies in plasma and with the development of anemia in these patients. No association of anti-PS antibodies or anemia with other B-cell subsets or of other antibody specificities with FcRL5+T-bet+B-cells is observed, revealing high specificity in this response. We also identify FcRL5+T-bet+B-cells as producers of anti-PS antibodies in ex vivo cultures of naive human PBMC stimulated with P. falciparum-infected erythrocyte lysates. These data define a crucial role for atypical memory B-cells and anti-PS autoantibodies in human malarial anemia.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

  1. Juan Rivera-Correa

    Department of Microbiology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Sophia Mackroth

    Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Jacobs

    Protozoa Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Julian Schulze zur Wiesch

    Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Thierry Rolling

    Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Ana Rodriguez

    Department of Microbiology, New York University School of Medicine, New York, United States
    For correspondence
    ana.rodriguez@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0060-3405

Funding

National Institute of Allergy and Infectious Diseases (5T32AI100853)

  • Juan Rivera-Correa

National Institute of Allergy and Infectious Diseases (5T32AI007180)

  • Juan Rivera-Correa

Deutsches Zentrum für Infektionsforschung (TI07.001_Rolling)

  • Thierry Rolling

National Center for Advancing Translational Sciences (1UL1TR001445)

  • Ana Rodriguez

National Center for Advancing Translational Sciences (1KL2 436 TR001446)

  • Ana Rodriguez

National Center for Advancing Translational Sciences (1TL1 TR001447)

  • Ana Rodriguez

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

Ethics

Human subjects: Patients were recruited at the University Medical Center Hamburg-Eppendorf. Inclusion criteria were age between 18 and 65 years, hemoglobin >8g/dl and a diagnosis of P. falciparum malaria by microscopy. All individuals gave written informed consent. Participant data was transmitted to the United States after double pseudoanonymization and without any protected health information. The study protocol was approved by the Ethics committee of the Hamburg Medical Association (PV4539).

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: May 9, 2019
  2. Accepted: October 27, 2019
  3. Accepted Manuscript published: November 12, 2019 (version 1)
  4. Version of Record published: November 13, 2019 (version 2)

Copyright

© 2019, Rivera-Correa 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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