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

• Type of Material: Article
• Authors: Silvia Portugal, National Institutes of Health; Christopher M. Tipton, Emory University; Haewon Sohn, National Institutes of Health; Younoussou Kone, Univ Sci Tech & Technol Bamako; Jing Wang, National Institutes of Health; Shanping Li, National Institutes of Health; Jeff Skinner, National Institutes of Health; Kimmo Virtaneva, National Institutes of Health; Daniel E Sturdevant, National Institutes of Health; Stephen F Porcella, National Institutes of Health; Ogobara K Doumbo, University of Sciences, Technique and Technology of Bamako; Safiatou Doumbo, University of Sciences, Technique and Technology of Bamako; Kassoum Kayentao, University of Sciences, Technique and Technology of Bamako; Aissata Ongoiba, University of Sciences, Technique and Technology of Bamako; Boubacar Traore, University of Sciences, Technique and Technology of Bamako; Ignacio Sanz, Emory University; Susan K Pierce, National Institutes of Health; Peter D Crompton, National Institutes of Health
• Language: English
• Date: 2015-05-08
• Publisher: eLife Sciences Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2015, eLife Sciences Publications Ltd. All rights reserved.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.07218
• Title of Journal or Parent Work: eLife
• ISSN: 2050-084X
• Volume: 4
• Issue: MAY
• Grant/Funding Information: National Institutes of Health (NIH) to Peter D Crompton.; This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.; This paper was supported by the following grants: Division of Intramural Research, National Institute of Allergy and Infectious Diseases Z01 AI000949-02 LIG to Peter D Crompton.
• Keywords: PROLIFERATION; ENDEMIC AREA; Life Sciences & Biomedicine - Other Topics; PROMOTES; UNSTABLE MALARIA; ACTIVATION; Biology; INDIVIDUALS; Life Sciences & Biomedicine; PLASMODIUM-FALCIPARUM; MEROZOITE; ANTIBODY-RESPONSES; Science & Technology; TRANSMISSION
• Research Categories: Health Sciences, General; Health Sciences, Immunology

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.