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J Immunol. 2005 Jun 1;174(11):6781-90.

Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptor.

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1
Trudeau Institute, Saranac Lake, NY 12983, USA.

Abstract

This manuscript systematically identifies the molecular mechanisms that regulate the ability of B cells to produce the critical type 1 cytokine, IFN-gamma. B cells produce IFN-gamma in response to IL-12 and IL-18 and when primed by Th1 cells. We show that development of IFN-gamma-producing B cells by either Th1 cells or IL-12/IL-18 is absolutely dependent on expression of the IFN-gammaR and the T-box transcription factor, T-bet. Interestingly, although T-bet up-regulation in developing B effector 1 (Be1) cells is controlled by IFN-gammaR-mediated signals, STAT1-deficient B cells up-regulate T-bet and produce IFN-gamma, indicating that additional transcriptional activators must be coupled to the IFN-gammaR in B cells. Finally, we show that although IL-12/IL-18 or IFN-gamma-producing Th1 cells are required to initiate transcription of the IFN-gamma gene in B cells, sustained expression of IFN-gamma and T-bet by B cells is dependent on an IFN-gamma/IFN-gammaR/T-bet autocrine feedback loop. These findings have significant implications, because they suggest that IFN-gamma-producing B cells not only amplify Th1 responses, but also imprint a type 1 phenotype on B cells themselves. In the case of immune responses to bacterial or viral pathogens, this B cell-driven autocrine feedback loop is likely to be beneficial; however, in the case of B cell responses to autoantigens, it may result in amplification of the autoimmune loop and increased pathology.

PMID:
15905519
[Indexed for MEDLINE]
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