Activation-induced Deaminase (AID)-directed Hypermutation in the Immunoglobulin S{micro} Region: Implication of AID Involvement in a Common Step of Class Switch Recombination and Somatic Hypermutation

doi:10.1084/jem.20012144

Published 19 February 2002. doi:10.1084/jem.20012144

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© Rockefeller University Press, 0022-1007/2002/2/529/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 4, February 18, 2002 529-534

Brief Definitive Report

Activation-induced Deaminase (AID)-directed Hypermutation in the Immunoglobulin Sµ Region : Implication of AID Involvement in a Common Step of Class Switch Recombination and Somatic Hypermutation

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 immunoglobulingenes in B lymphocytes: point mutations in variable regionsand large deletions in S regions, respectively. Yet both dependon activation-induced deaminase (AID), the function of whichin the two reactions has been an enigma. Here we report thatB cell stimulation which induces CSR but not SHM, leads to AID-dependentaccumulation of SHM-like point mutations in the switch µregion, uncoupled with CSR. These findings strongly suggestthat AID itself or a single molecule generated by RNA editingfunction of AID may mediate a common step of SHM and CSR, whichis likely to be involved in DNA cleavage.

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

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