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Separate domains of AID are required for somatic hypermutation and class-switch recombination

Nature Immunology volume 5, pages 707–712 (2004)Cite this article

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Abstract

Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM). Mutants with changes in the C-terminal region of AID retain SHM but lose CSR activity. Here we describe five mutants with alterations in the N-terminal region of AID that caused selective deficiency in SHM but retained CSR, suggesting that the CSR and SHM activities of AID may dissociate via interaction of CSR- or SHM-specific cofactors with different domains of AID. Unlike cells expressing C-terminal AID mutants, B cells expressing N-terminal AID mutants had mutations in the switch μ region, indicating that such mutations are generated by reactions involved in CSR but not SHM. Thus, we propose that separate domains of AID interact with specific cofactors to regulate these two distinct genetic events in a target-specific way.

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Figure 1: N-terminal AID mutants show the SHM-specific loss of function.
Figure 2: Subcellular localization of wild-type or N-terminal mutant AID.
Figure 3: Chromatin immunoprecipitation analysis of CSR-dependent γ-H2AX focus formation at the Igh locus.

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  • 20 June 2004

    added erratum PDF to AOP PDF, added note to XML, and corrected online date will be included in the issue PDF

Notes

  1. *Note: In the version of this article originally published online, the values for "Total base number" in Table 4 were incomplete. The correct numbers are as follows: 24,487; 25,008; 23,445; 10,420; and 20,840. Line 3 of the legend for Figure 1 should read "mAID, mouse AID," and line 1 of the legend to Table 2 legend should begin "DNA". This error has been corrected for the HTML and print versions of this article.

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Acknowledgements

We thank J.C. Weill and C.A. Reynaud for providing BL2 cells; S. Fagarasan for critical comments and reading the manuscript; E. Inoue, Y. Sasaki and Y. Hosoe for technical assistance; and Y. Shiraki for preparation of the manuscript. Supported by Ministry of Education, Science, Sports, and Culture of Japan (Center of Excellence Grant).

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  1. Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan

    Reiko Shinkura, Satomi Ito, Nasim A Begum, Hitoshi Nagaoka, Masamichi Muramatsu, Kazuo Kinoshita, Yoshimasa Sakakibara, Hiroko Hijikata & Tasuku Honjo

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  1. Reiko Shinkura
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Correspondence to Tasuku Honjo.

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Shinkura, R., Ito, S., Begum, N. et al. Separate domains of AID are required for somatic hypermutation and class-switch recombination. Nat Immunol 5, 707–712 (2004). https://doi.org/10.1038/ni1086

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