Cutting edge: STAT6 serves as a positive and negative regulator of gene expression in IL-4-stimulated B lymphocytes

J Immunol. 2002 Feb 1;168(3):996-1000. doi: 10.4049/jimmunol.168.3.996.

Abstract

STAT6 plays an important role in IL-4-mediated B cell activation and differentiation. To identify primary and secondary target genes of STAT6, gene expression profiles of IL-4-stimulated B cells from STAT6+/+ vs STAT6-/- mice were compared. Statistical analysis revealed that 106 distinct probe sets including 70 known genes were differentially expressed between the 2 genotypes. These genes include transcription factors, kinases, and other enzymes, cell surface receptors, and Ig H chains. Surprisingly, although 31 genes were expressed at higher levels in STAT6+/+ B cells, 39 genes were expressed at higher abundance in STAT6-/- B cells. This result implies both positive and negative regulatory functions of STAT6 in IL-4-mediated gene expression. Furthermore, IL-4 induces expression of the transcription factor Krox20, which is required for maximal IL-4-induced transcription.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Drug Combinations
  • Early Growth Response Protein 2
  • Gene Expression Regulation / immunology*
  • Interleukin-4 / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, IgE / biosynthesis
  • Receptors, IgE / genetics
  • STAT6 Transcription Factor
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transduction, Genetic
  • Up-Regulation / genetics
  • Up-Regulation / immunology*

Substances

  • DNA-Binding Proteins
  • Drug Combinations
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • Lipopolysaccharides
  • Receptors, IgE
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Interleukin-4