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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 ε 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-β1 (TGF-β1) and suppresses IgE CSR. Our results provide evidence for the inhibitory and selective role of Id2 in IgE CSR in response to TGF-β1. 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.

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We are grateful to K. Ikuta for discussions, H. Karasuyama for X63mIL3, A. Kudo for mPax5 expression plasmid, T. Kitamura for pMX-IRESGFP plasmid and G. P. Nolan for Phoenix Eco cells. We thank T. Ofuji for technical assistance. Supported in part by Grants-in-Aid for Scientific Research including ones on Priority Areas 'Genome Biology' (13206035, 14014220) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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The authors declare no competing financial interests.

Correspondence to Akira Shimizu.

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Figure 1: Enhanced IgE class switching in the spleen.
Figure 2: Enhanced IgE class switching in Id2−/− B cells.
Figure 3: Transactivation of the GLε promoter by E2A transcription factors.
Figure 4: Binding of the GLε promoter by E2A transcription factors.
Figure 5: Reintroduction of Id2 protein restores enhanced IgE class switching.
Figure 6: Id2 is induced by TGF-β1 in splenic B cells.
Figure 7: Inhibition of IgE CSR by TGF-β1 is mediated by Id2.