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International Immunology Advance Access originally published online on February 25, 2008
International Immunology 2008 20(4):499-508; doi:10.1093/intimm/dxn009
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© The Author 2008. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

PI3K is a negative regulator of IgE production

Tomomitsu Doi1,2,4, Kunie Obayashi1,5, Takashi Kadowaki2,3, Hideki Fujii1,2 and Shigeo Koyasu1,2

1 Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
2 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan
3 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
4 Present address: Department of Immunology and Genomic Medicine, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-6501, Japan
5 Present address: Department of Pharmacology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-6501, Japan

Correspondence to: S. Koyasu; E-mail: koyasu{at}sc.itc.keio.ac.jp

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 p85{alpha} regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85{alpha}–/– 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.

Keywords: AID, class switch recombination, Id2, IC87114, IgE, PI3K, wortmannin

Transmitting editor: T. Kurosaki

Received 17 September 2007, accepted 11 January 2008.


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