IFN-gamma-mediated inhibition of antigen receptor-induced B cell proliferation and CREB-1 binding activity requires

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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

Frank Frissora1, Hui-Chen Chen, Joan Durbin

  • 1Children's Research Institute, Wexner Institute for Pediatric Research, Columbus, OH 43205, USA.

European Journal of Immunology
|April 3, 2003
PubMed

Insights

Interferon-gamma (IFN-gamma) inhibits B cell proliferation by regulating cyclic AMP-responsive element-binding protein-1 (CREB-1) DNA binding. This pathway requires signal transducer and activator of transcription-1 (STAT-1) for negative regulation of B cell activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • B cell antigen receptor (BCR) signaling regulates B cell proliferation.
  • Interferon-gamma (IFN-gamma) acts as a negative regulator of BCR-induced proliferation.
  • Cyclic AMP-responsive element-binding protein-1 (CREB-1) is a transcription factor involved in cellular responses.

Purpose of the Study:

  • To investigate the role of CREB-1 in IFN-gamma-mediated negative regulation of BCR-induced B cell growth.
  • To elucidate the signaling cross-talk between CREB-1 and signal transducer and activator of transcription-1 (STAT-1) pathways in B cells.

Main Methods:

  • Stimulation of B cells through BCR.
  • Assessment of CREB-1 DNA binding activity using electrophoretic mobility shift assays.
  • Analysis of cell proliferation in response to IFN-gamma.
  • Comparison of responses in STAT-1 proficient and deficient B cells.

Main Results:

  • BCR stimulation induced CREB-1 binding to its consensus element in a dose-dependent manner.
  • Recombinant IFN-gamma inhibited BCR-induced CREB-1 DNA binding activity.
  • IFN-gamma also inhibited BCR-induced B cell proliferation in STAT-1(+/+) B cells, but not in STAT-1(-/-) B cells.
  • These findings indicate a dependence on STAT-1 for IFN-gamma's inhibitory effects.

Conclusions:

  • CREB-1 plays a crucial role in IFN-gamma-mediated inhibition of BCR-induced B cell proliferation.
  • Cross-talk exists between STAT-1 and CREB-1 signaling pathways in the context of IFN-gamma's regulatory function on B cell activation.
  • This study reveals a novel mechanism for controlling B cell responses through the interplay of these signaling molecules.

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