IFN-gamma-mediated inhibition of antigen receptor-induced B cell proliferation and CREB-1 binding activity requires STAT-1 transcription factor.
We report here a role for cyclic AMP-responsive element-binding protein-1 (CREB-1) in B cell antigen receptor (BCR)-induced growth inhibition by IFN-gamma. BCR-induced proliferation is negatively regulated by IFN-gamma. Stimulation through BCR resulted in dose-dependent induction of CREB-1 binding to the consensus cyclic AMP-responsive element. Recombinant IFN-gamma inhibited the BCR-induced CREB-1 DNA binding activity and cell proliferation in B cells from signal transducer and activator of transcription-1 (STAT-1)(+/+), but not STAT-1(-/-) mice. These studies provide the first evidence for cross-talk between the STAT-1 and CREB-1 signaling pathways in IFN-gamma-mediated negative regulation of B cell activation.
Frissora
Frank
F
Children's Research Institute, Wexner Institute for Pediatric Research, Columbus, OH 43205, USA.
Chen
Hui-Chen
HC
Durbin
Joan
J
Bondada
Subbarao
S
Muthusamy
Natarajan
N
D051698:Activating Transcription Factor 2; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D011947:Receptors, Antigen, B-Cell; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma