Essential role of Id2 in negative regulation of IgE class switching.
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.
Sugai
Manabu
M
Center for Molecular Biology and Genetics, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Gonda
Hiroyuki
H
Kusunoki
Takashi
T
Katakai
Tomoya
T
Yokota
Yoshifumi
Y
Shimizu
Akira
A
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics*; D066298:In Vitro Techniques; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D007073:Immunoglobulin E; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C497450:ID2 protein, human; C497452:Idb2 protein, mouse; C407909:TCF3 protein, human; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse