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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2017-09-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1006576

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.