Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies
- New York University School of Medicine, United States
- University Medical Center Hamburg-Eppendorf, Germany
- Bernhard Nocht Institute for Tropical Medicine, Germany
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.
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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
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).
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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Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies
eLife 8:e48309.
https://doi.org/10.7554/eLife.48309
