| First Author | Harris DP | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 11 | Pages | 6781-90 |
| PubMed ID | 15905519 | Mgi Jnum | J:99038 |
| Mgi Id | MGI:3580991 | Doi | 10.4049/jimmunol.174.11.6781 |
| Citation | Harris DP, et al. (2005) Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptor. J Immunol 174(11):6781-90 |
| abstractText | 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. |
