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

• Verfasst von: Obeng-Adjei, Nyamekye [VerfasserIn]
• Verfasst von: Portugal, Silvia [VerfasserIn]
• Titel: Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells
• Verf.angabe: Nyamekye Obeng-Adjei, Silvia Portugal, Prasida Holla, Shanping Li, Haewon Sohn, Abhijit Ambegaonkar, Jeff Skinner, Georgina Bowyer, Ogobara K. Doumbo, Boubacar Traore, Susan K. Pierce, Peter D. Crompton
• Fussnoten: Im Titel sind beim Begriff "Tbethi" die Zeichen "hi" hochgestellt ; Gesehen am 13.09.2018
• Titel Quelle: Enthalten in: Public Library of Science: PLoS pathogens
• Jahr Quelle: 2017
• Band/Heft Quelle: 13(2017,9) Artikel-Nummer e1006576, 30 Seiten
• ISSN Quelle: 1553-7374
• DOI: doi:10.1371/journal.ppat.1006576
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580958400

Abstract

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.