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

Abstract

CpG DNA has immunomodulatory effects, such as the suppression of allergic responses mediated by type II T cell help (TH2). 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-γ (IFN-γ)-STAT1 and synergistic with IL-12.

*Note: In the version of this article initially published online, some of the nomenclature was incorrect. This has been corrected for the HTML and print versions of the article.

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Change history

  • 15 June 2003

    appended aop PDF with erratum (will be corrected for print issue), and placed footnote in SGML at abstract

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Acknowledgements

We thank K. Nakashima and Y. Manabe for experimental assistance and J. Encinas for valuable discussions.

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Correspondence to Ningshu Liu.

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The authors declare no competing financial interests.

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Figure 1: Induction of T-bet in mouse splenocytes.
Figure 2: Stimulus-induced STAT1α/β phosphorylation in splenocytes.
Figure 3: T-bet transactivation and STAT1 phosphorylation in MyD88- or TLR9-deficient mice.
Figure 4: Cell types expressing T-bet in response to CpG.
Figure 5: CpG-induced, IFN-γ–STAT1-independent expression of T-bet in purified B cells.
Figure 6: Characterization of signal cascades involved in CpG-induced T-bet transactivation in purified B cells.
Figure 7: Inhibition of IL-4– and CD40-ligation–induced IgG1, IgG2a and IgE production.