| First Author | Hock M | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 5 | Pages | 2345-53 |
| PubMed ID | 23365084 | Mgi Jnum | J:346787 |
| Mgi Id | MGI:6839758 | Doi | 10.4049/jimmunol.1201591 |
| Citation | Hock M, et al. (2013) NFATc1 induction in peripheral T and B lymphocytes. J Immunol 190(5):2345-53 |
| abstractText | NFAT transcription factors control the proliferation and survival of peripheral lymphocytes. We have reported previously that the short isoform NFATc1/alphaA whose generation is induced by immune receptor stimulation supports the proliferation and inhibits the activation-induced cell death of peripheral T and B cells. We will show in this study that in novel bacterial artificial chromosome transgenic mice that express EGFP under the control of entire Nfatc1 locus the Nfatc1/Egfp transgene is expressed as early as in double-negative thymocytes and in nonstimulated peripheral T and B cells. Upon immune receptor stimulation, Nfatc1/Egfp expression is elevated in B, Th1, and Th2 cells, but only weakly in T regulatory, Th9, and Th17 cells in vitro whose generation is affected by TGFbeta. In naive lymphocytes, persistent immune receptor signals led to a 3-5 increase in NFATc1/alphaA RNA levels during primary and secondary stimulation, but a much stronger induction was observed at the protein level. Whereas anti-CD3(+)CD28 stimulation of primary T cells induces both NFATc1/alphaA and their proliferation and survival, anti-IgM stimulation of B cells induces NFATc1/alphaA and proliferation, but activation-induced cell death after 3-d incubation in vitro. The anti-IgM-mediated activation-induced cell death induction of B cells in vitro is suppressed by anti-CD40-, LPS-, and CpG-mediated signals. In addition to inducing NF-kappaB factors, together with anti-IgM, these signals also support the generation of NFATc1/alphaA. According to these data and the architecture of its promoter region, the Nfatc1 gene resembles a primary response gene whose induction is affected at the posttranscriptional level. |
