Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells
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 a...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 27, 2017
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| In: |
PLoS pathogens
Year: 2017, Volume: 13, Issue: 9 |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1006576 |
| Online Access: | Resolving-System, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.ppat.1006576 Verlag, kostenfrei, Volltext: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006576 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Im Titel sind beim Begriff "Tbethi" die Zeichen "hi" hochgestellt Gesehen am 13.09.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1006576 |