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Brief Definitive Report

Hitoshi Nagaoka, Masamichi Muramatsu, Namiko Yamamura, Kazuo Kinoshita and Tasuku Honjo

Department of Medical Chemistry Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

Address correspondence to T. Honjo, Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan. Phone: 81-75-753-4371; Fax: 81-75-753-4388; E-mail: honjo{at}mfour.med.kyoto-u.ac.jp

Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch µ region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.

Key Words: B lymphocyte • immunoglobulin gene • heavy chain • DNA cleavage • error-prone repair

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