Regulation of IFN-γ Production by B Effector 1 Cells: Essential Roles for T-bet and the IFN-γ Receptor
In: The Journal of Immunology, Jg. 174 (2005-06-01), S. 6781-6790
Online
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Zugriff:
This manuscript systematically identifies the molecular mechanisms that regulate the ability of B cells to produce the critical type 1 cytokine, IFN-γ. B cells produce IFN-γ in response to IL-12 and IL-18 and when primed by Th1 cells. We show that development of IFN-γ-producing B cells by either Th1 cells or IL-12/IL-18 is absolutely dependent on expression of the IFN-γR 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-γR-mediated signals, STAT1-deficient B cells up-regulate T-bet and produce IFN-γ, indicating that additional transcriptional activators must be coupled to the IFN-γR in B cells. Finally, we show that although IL-12/IL-18 or IFN-γ-producing Th1 cells are required to initiate transcription of the IFN-γ gene in B cells, sustained expression of IFN-γ and T-bet by B cells is dependent on an IFN-γ/IFN-γR/T-bet autocrine feedback loop. These findings have significant implications, because they suggest that IFN-γ-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.
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Regulation of IFN-γ Production by B Effector 1 Cells: Essential Roles for T-bet and the IFN-γ Receptor
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Autor/in / Beteiligte Person: | Gerth, Andrea J. ; Peng, Stanford L. ; Harris, David P. ; Lund, Frances E. ; Goodrich, Stephen |
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Zeitschrift: | The Journal of Immunology, Jg. 174 (2005-06-01), S. 6781-6790 |
Veröffentlichung: | The American Association of Immunologists, 2005 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.174.11.6781 |
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