Essential role of Id2 in negative regulation of IgE class switching

Manabu Sugai; Hiroyuki Gonda; Takashi Kusunoki; Tomoya Katakai; Yoshifumi Yokota; Akira Shimizu

doi:10.1038/ni874

Essential role of Id2 in negative regulation of IgE class switching

Nat Immunol. 2003 Jan;4(1):25-30. doi: 10.1038/ni874. Epub 2002 Dec 16.

Authors

Manabu Sugai¹, Hiroyuki Gonda, Takashi Kusunoki, Tomoya Katakai, Yoshifumi Yokota, Akira Shimizu

Affiliation

¹ Center for Molecular Biology and Genetics, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

PMID: 12483209
DOI: 10.1038/ni874

Abstract

Serum concentrations of immunoglobulin E (IgE) in normal circumstances are kept much lower than those of other Ig isotypes to avoid allergic reactions. B cells lacking Id2 have increased E2A activity, which leads to specific enhancement of germline transcription of the immunoglobulin epsilon locus. As a consequence, Id2-deficient B cells undergo class switch recombination (CSR) to IgE at a much higher frequency than wild-type B cells. In contrast, Id2 is induced in wild-type B cells by transforming growth factor-beta1 (TGF-beta1) and suppresses IgE CSR. Our results provide evidence for the inhibitory and selective role of Id2 in IgE CSR in response to TGF-beta1. Id2 might act as molecular safeguard to suppress IgE CSR to prevent serious complications such as allergic hypersensitivity during the normal course of immune responses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes / drug effects
B-Lymphocytes / immunology
Base Sequence
Basic Helix-Loop-Helix Transcription Factors
DNA / genetics
DNA / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism*
Humans
Hypersensitivity / genetics
Hypersensitivity / immunology
Immunoglobulin Class Switching* / drug effects
Immunoglobulin E / biosynthesis*
Immunoglobulin E / genetics*
In Vitro Techniques
Inhibitor of Differentiation Protein 2
Mice
Mice, Knockout
Promoter Regions, Genetic
Protein Binding
Repressor Proteins*
Transcription Factors / genetics*
Transcription Factors / metabolism*
Transcriptional Activation
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta1

Substances

Basic Helix-Loop-Helix Transcription Factors
DNA-Binding Proteins
ID2 protein, human
Idb2 protein, mouse
Inhibitor of Differentiation Protein 2
Repressor Proteins
TCF3 protein, human
TGFB1 protein, human
Tgfb1 protein, mouse
Transcription Factors
Transforming Growth Factor beta
Transforming Growth Factor beta1
Immunoglobulin E
DNA