Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function
- National Institutes of Health, United States
- Emory University, United States
- University of Sciences, Technique and Technology of Bamako, Mali
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.
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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.
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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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Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function
eLife 4:e07218.
https://doi.org/10.7554/eLife.07218
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