期刊论文详细信息
PLoS Pathogens | |
Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells | |
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 | |
[2]Lymphocyte Activation Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America | |
[3]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 | |
[4]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 | |
[5]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 | |
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【 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
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