PI3K is a negative regulator of IgE production

Tomomitsu Doi, Kunie Obayashi, Takashi Kadowaki, Hideki Fujii, Shigeo Koyasu

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85α regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85α-/- B cells produced more IgE than wild-type B cells in vitro in response to anti-CD40 mAb and IL-4. PI3K inhibitors wortmannin and IC87114 enhanced IgE production by wild-type B cells stimulated with anti-CD40 mAb and IL-4. Under the same condition, antigen receptor cross-linking induced the expression of inhibitor of differentiation-2 and suppressed the expression of activation-induced cytidine deaminase and class switch recombination (CSR) in a PI3K-dependent manner. IgE production was also suppressed in a concentrated cell culture condition, which was completely reversed by PI3K inhibition. The selective suppression of IgE production by PI3K was also observed at a protein level after CSR. Our results indicate that PI3K negatively regulates IgE production at both CSR and protein levels.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalInternational immunology
Volume20
Issue number4
DOIs
Publication statusPublished - 2008 Apr

Keywords

  • AID
  • Class switch recombination
  • IC87114
  • Id2
  • IgE
  • PI3K
  • Wortmannin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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