CD86 and β2-adrenergic receptor signalling pathways, respectively, increase Oct-2 and OCA-B expression and binding to the 3′-IgH enhancer in B cells

Joseph R. Podojil, Nicholas W. Kin, Virginia M. Sander*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Stimulation of CD86 (formerly known as B7-2) and/or the β 2-adrenergic receptor on a CD46 ligand/interleukin-4-activated B cell increased the rate of mature IgG1 transcription. To identify the mechanism responsible for this effect, we determined whether CD86 and/or β2-adrenergic receptor stimulation regulated transcription factor expression and binding to the 3′-IgH enhancer in vitro and in vivo. We showed that CD86 stimulation increased the nuclear localization of NF-κB1 (p50) and phosphorylated RelA (p65) and increased Oct-2 expression and binding to the 3′-IgH enhancer, in a protein kinase C-dependent manner. These effects were lost when CD86-deficient of NF-κB1-deficient B cells were used. CD86 stimulation also increased the level of IκB-α phosphorylation but in a protein kinase C-independent manner. β 2-Adrenergic receptor stimulation increased CREB phosphorylation, OCA-B expression, and OCA-B binding to the 3′-IgH enhancer in a protein kinase A-dependent manner, an effect lost when β2-adrenergic receptor-deficient B cells were used. Also, the β2-adrenergic receptor-induced increase in the level of mature IgG1 transcript, was lost when OCA-B-deficient B cells were used. These data are the first to show that CD86 stimulation up-regulates the expression of the transcription factor Oct-2 in a protein kinase C- and NF-κB1-dependent manner, and that β2-adrenergic receptor stimulation up-regulates the expression of the coactivator OCA-B in a protein kinase A-dependent manner to cooperate with Oct-2 binding to the 3′-IgH enhancer.

Original languageEnglish (US)
Pages (from-to)23394-23404
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number22
DOIs
StatePublished - May 28 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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