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Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells.
- Source :
-
PLoS Pathogens . 9/27/2017, Vol. 13 Issue 9, p1-30. 30p. - Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MALARIA
*INTERFERON gamma
*B cells
*GENE expression
*T helper cells
*IMMUNE system
Subjects
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 13
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 125368662
- Full Text :
- https://doi.org/10.1371/journal.ppat.1006576