CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells

Nat Immunol. 2003 Jul;4(7):687-93. doi: 10.1038/ni941. Epub 2003 May 25.

Abstract

CpG DNA has immunomodulatory effects, such as the suppression of allergic responses mediated by type II T cell help (T(H)2). Here we report that CpG, but not lipopolysaccharide (LPS), rapidly induces expression of T-bet mRNA in purified B cells. Up-regulation of T-bet by CpG is abrogated in mice deficient in Toll-like receptor 9 (TLR9) and MyD88, but remains intact in B cells deficient in STAT1 (signal transducer and activator of transcription 1). Interleukin 12 (IL-12) alone does not up-regulate T-bet mRNA, but greatly enhances CpG-induced T-bet expression. Furthermore, CpG inhibits immunoglobulin G1 (IgG1) and IgE switching induced by IL-4 and CD40 signaling in purified B cells, and this effect correlates with up-regulation of T-bet. Thus, CpG triggers anti-allergic immune responses by directly regulating T-bet expression via a signaling pathway in B cells that is dependent upon TLR9, independent of interferon-gamma (IFN-gamma)-STAT1 and synergistic with IL-12.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Gene Expression Regulation / drug effects*
  • Immunoglobulin Class Switching / drug effects*
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / classification
  • Interferon-gamma / physiology
  • Interleukin-12 / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / physiology
  • NF-kappa B / physiology
  • Oligodeoxyribonucleotides / pharmacology*
  • Receptors, Cell Surface / physiology
  • Recombination, Genetic
  • STAT1 Transcription Factor
  • T-Box Domain Proteins
  • Toll-Like Receptor 9
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

Substances

  • CPG-oligonucleotide
  • DNA-Binding Proteins
  • Immunoglobulin G
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • Trans-Activators
  • Transcription Factors
  • Interleukin-12
  • Immunoglobulin E
  • Interferon-gamma
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases