1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

  1. Silvia Portugal
  2. Christopher M Tipton
  3. Haewon Sohn
  4. Younoussou Kone
  5. Jing Wang
  6. Shanping Li
  7. Jeff Skinner
  8. Kimmo Virtaneva
  9. Daniel E Sturdevant
  10. Stephen F Porcella
  11. Ogobara K Doumbo
  12. Safiatou Doumbo
  13. Kassoum Kayentao
  14. Aissata Ongoiba
  15. Boubacar Traore
  16. Inaki Sanz
  17. Susan K Pierce
  18. Peter D Crompton  Is a corresponding author
  1. National Institutes of Health, United States
  2. Emory University, United States
  3. University of Sciences, Technique and Technology of Bamako, Mali
Research Article
  • Cited 124
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Cite this article as: eLife 2015;4:e07218 doi: 10.7554/eLife.07218

Abstract

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity.

Article and author information

Author details

  1. Silvia Portugal

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher M Tipton

    Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Haewon Sohn

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Younoussou Kone

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  5. Jing Wang

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shanping Li

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jeff Skinner

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kimmo Virtaneva

    Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Daniel E Sturdevant

    Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Stephen F Porcella

    Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Ogobara K Doumbo

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  12. Safiatou Doumbo

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  13. Kassoum Kayentao

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  14. Aissata Ongoiba

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  15. Boubacar Traore

    Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
    Competing interests
    The authors declare that no competing interests exist.
  16. Inaki Sanz

    Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Susan K Pierce

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter D Crompton

    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
    For correspondence
    pcrompton@niaid.nih.gov
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: The Ethics Committee of the Faculty of Medicine, Pharmacy, and Dentistry at the University of Sciences, Techniques, and Technologies of Bamako, and the Institutional Review Board of the National Institute of Allergy and Infectious Diseases, National Institutes of Health approved this study. Written informed consent and consent to publish was received from participants prior to inclusion in the study. Written informed consent and consent to publish was obtained from parents or guardians of participating children prior to inclusion in the study. NIAID IRB protocols 07-I-N141 or 06-I-N147.

Reviewing Editor

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

Publication history

  1. Received: February 27, 2015
  2. Accepted: May 6, 2015
  3. Accepted Manuscript published: May 8, 2015 (version 1)
  4. Version of Record published: May 27, 2015 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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