NFATc1 induction in peripheral T and B lymphocytes

Matthias Hock, Martin Vaeth, Ronald Rudolf, Amiya Kumar Patra, Duong Anh Thuy Pham, Khalid Muhammad, Tobias Pusch, Tobias Bopp, Edgar Schmitt, Rene Rost, Friederike Berberich-Siebelt, Dimitri Tyrsin, Sergei Chuvpilo, Andris Avots, Edgar Serfling, Stefan Klein-Hessling

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

NFAT transcription factors control the proliferation and survival of peripheral lymphocytes.We have reported previously that the short isoform NFATc1/aAwhose 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 TGFβ. In naive lymphocytes, persistent immune receptor signals led to a 3-5 increase in NFATc1/αA 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/αA and their proliferation and survival, anti-IgM stimulation of B cells induces NFATc1/αA 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-κB factors, together with anti-IgM, these signals also support the generation of NFATc1/αA. 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.

Original languageEnglish
Pages (from-to)2345-2353
Number of pages9
JournalJournal of Immunology
Volume190
Issue number5
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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