The Journal of Experimental Medicine
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Published online 27 October 2003 doi:10.1084/jem.20030802
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© Rockefeller University Press, 0022-1007/2003/11/1427 $5.00
The Journal of Experimental Medicine, Volume 198, Number 9, 1427-1437

The Balance Between Pax5 and Id2 Activities Is the Key to AID Gene Expression

Hiroyuki Gonda1,2, Manabu Sugai1, Yukiko Nambu1, Tomoya Katakai1, Yasutoshi Agata1, Kazuhiro J. Mori3, Yoshifumi Yokota4 and Akira Shimizu1,2

1 Center for Molecular Biology and Genetics, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
2 Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan
3 Department of Biology, Faculty of Science, Niigata University, Niigata 950-2181, Japan
4 Department of Biochemistry, Fukui Medical University, Matsuoka, Fukui 910-1193, Japan

Address correspondence to Manabu Sugai, Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4719; Fax: 81-75-751-4731; e-mail: msugai{at}virus.kyoto-u.ac.jp

Pax5 activity is enhanced in activated B cells and is essential for class switch recombination (CSR). We show that inhibitor of differentiation (Id)2 suppresses CSR by repressing the gene expression of activation-induced cytidine deaminase (AID), which has been shown to be indispensable for CSR. Furthermore, a putative regulatory region of AID contains E2A- and Pax5-binding sites, and the latter site is indispensable for AID gene expression. Moreover, the DNA-binding activity of Pax5 is decreased in Id2-overexpressing B cells and enhanced in Id2-/- B cells. The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as AID expression in primary B cells. Finally, enforced expression of Pax5 induces AID transcription in pro–B cell lines. Our results provide evidence that the balance between Pax5 and Id2 activities has a key role in AID gene expression.

Key Words: B cell activation • class switch recombination • chromatin immunoprecipitation • histone acetylation • transcription


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