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Elife. 2015 May 8;4. doi: 10.7554/eLife.07218.

Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function.

Author information

1
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States.
2
Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States.
3
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.
4
Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States.

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.

KEYWORDS:

Plasmodium falciparum; atypical memory B cells; human; immunology; infectious disease; malaria; microbiology

PMID:
25955968
PMCID:
PMC4444601
DOI:
10.7554/eLife.07218
[Indexed for MEDLINE]
Free PMC Article

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