NFATc1 induction in peripheral T and B lymphocytes.
NFAT transcription factors control the proliferation and survival of peripheral lymphocytes. We have reported previously that the short isoform NFATc1/αA 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 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.
Department of Molecular Pathology, Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany.
Matthias
M
Hock
Martin
M
Vaeth
Ronald
R
Rudolf
Amiya Kumar
AK
Patra
Duong Anh Thuy
DA
Pham
Khalid
K
Muhammad
Tobias
T
Pusch
Tobias
T
Bopp
Edgar
E
Schmitt
Rene
R
Rost
Friederike
F
Berberich-Siebelt
Dimitri
D
Tyrsin
Sergei
S
Chuvpilo
Andris
A
Avots
Edgar
E
Serfling
Stefan
S
Klein-Hessling
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D050778:NFATC Transcription Factors / Q000819:agonists / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins