Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells

PLoS Pathogens

Prasida Holla¹  Jeff Skinner²  Shanping Li²  Abhijit Ambegaonkar²  Peter D. Crompton²  Silvia Portugal³  Georgina Bowyer³  Nyamekye Obeng-Adjei³  Haewon Sohn³  Boubacar Traore⁴  Susan K. Pierce⁴  Ogobara K. Doumbo⁵ 

[1] Center for Infectious Diseases, Parasitology, Heidelberg University Hospital, Heidelberg, Germany;Lymphocyte Activation Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America;Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America;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;The Jenner Institute Laboratories, University of Oxford, Oxford, United Kingdom

关键词: B cells;    Malaria;    Cytokines;    Cross-linking;    B cell receptors;    Cell differentiation;    T cells;    Children;   

DOI  :  10.1371/journal.ppat.1006576

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Many chronic infections, including malaria and HIV, are associated with a large expansion of CD21−CD27− ‘atypical’ memory B cells (MBCs) that exhibit reduced B cell receptor (BCR) signaling and effector functions. Little is known about the conditions or transcriptional regulators driving atypical MBC differentiation. Here we show that atypical MBCs in malaria-exposed individuals highly express the transcription factor T-bet, and that T-bet expression correlates inversely with BCR signaling and skews toward IgG3 class switching. Moreover, a longitudinal analysis of a subset of children suggested a correlation between the incidence of febrile malaria and the expansion of T-bethi B cells. The Th1-cytokine containing supernatants of malaria-stimulated PBMCs plus BCR cross linking induced T-bet expression in naïve B cells that was abrogated by neutralizing IFN-γ or blocking the IFN-γ receptor on B cells. Accordingly, recombinant IFN-γ plus BCR cross-linking drove T-bet expression in peripheral and tonsillar B cells. Consistent with this, Th1-polarized Tfh (Tfh-1) cells more efficiently induced T-bet expression in naïve B cells. These data provide new insight into the mechanisms underlying atypical MBC differentiation.

【 授权许可】

CC BY