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International Immunology Advance Access originally published online on November 15, 2005
International Immunology 2006 18(1):41-47; doi:10.1093/intimm/dxh347
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID

Koshou Wakae1,*, Brad G. Magor2, Holly Saunders2, Hitoshi Nagaoka1, Akemi Kawamura1, Kazuo Kinoshita3, Tasuku Honjo1 and Masamichi Muramatsu1,*

1 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan
2 Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G-2E9, Canada
3 Department of Evolutionary Genetics, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan

Correspondence to: M. Muramatsu; E-mail: muramatu{at}mfour.med.kyoto-u.ac.jp

Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony fishes, and this may be due in part to a lack of cis-elements in the IgH gene that are the normal targets of AID-mediated recombination. We have tested whether bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells. As expected, ectopic expression of fish AID in mouse fibroblasts resulted in mutations in an introduced SHM reporter gene, indicating that fish AID can mediate SHM. Unexpectedly, expression of fish AID in mouse AID–/– B cells induced surface IgG expression as well as switched transcripts from Ig gene loci, clearly indicating that the fish AID protein can mediate CSR, at least in mouse cells. These results suggest that the AID protein acquired the ability to mediate CSR before the IgH locus evolved the additional exon clusters and switch regions that are the targets of recombination. We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates.

Keywords: APOBEC-1, B cells, class switch recombination, immunoglobulin gene, somatic hypermutation

Transmitting editor: T. Watanabe

* These authors contributed equally to this study.


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