Malaria-associated Atypical Memory B Cells Exhibit Markedly Reduced B Cell Receptor Signaling and Effector Function

Overview

Journal Elife

Specialty Biology

Date 2015 May 9

PMID 25955968

Citations 166

Authors

Silvia Portugal

Christopher M Tipton

Haewon Sohn

Younoussou Kone

Jing Wang

Shanping Li

Jeff Skinner

Kimmo Virtaneva

Daniel E Sturdevant

Stephen F Porcella

Ogobara K Doumbo

Safiatou Doumbo

Kassoum Kayentao

Aissata Ongoiba

Boubacar Traore

Inaki Sanz

Susan K Pierce

Peter D Crompton

Affiliations

Soon will be listed here.

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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