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AID mutant analyses indicate requirement for class-switch-specific cofactors

Nature Immunology volume 4, pages 843–848 (2003)Cite this article

Abstract

Activation-induced cytidine deaminase (AID) is the essential and sole B cell–specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two independent events. Involvement of several cofactors interacting with AID has been indicated by scattered distribution of loss-of-function point mutations and evolutionary conservation of the entire 198-amino-acid protein. Here, we report that human AID mutant proteins with insertions, replacements or truncations in the C-terminal region retained strong SHM activity but almost completely lost CSR activity. These results indicate that AID requires interaction with a cofactor(s) specific to CSR.

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Figure 1: Mapping of AID mutants and sequence conservation of AID.
Figure 2: In vitro AID mutant CSR and SHM activity.
Figure 3: Complex formation of AID.

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Acknowledgements

We thank M. Nakata, T. Toyoshima and E. Inoue for technical support; T. Nishikawa and Y. Shiraki for help in preparing the manuscript; S. Fagarasan, B. Meek and R. Shinkura for critical reading of the manuscript; and P. Lane for clinical support of patients. This investigation was supported by The Japan Society for the Promotion of Science (to V.-T.T.) and Center-of-Excellence grants from Minister of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

  1. Inserm U429, Hopital Necker-Enfants Malades, 149 Rue de Sevres, Paris, France

    Nadia Catalan, Anne Durandy, Alain Fischer & Kohsuke Imai

  2. Department of Pediatrics, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Saitama, Japan

    Shigeaki Nonoyama

  3. Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Kohsuke Imai & Shigeaki Nonoyama

  4. Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan

    Van-Thanh Ta, Hitoshi Nagaoka, Junko Tashiro, Masaya Ikegawa, Satomi Ito, Kazuo Kinoshita, Masamichi Muramatsu & Tasuku Honjo

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Correspondence to Tasuku Honjo.

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Ta, VT., Nagaoka, H., Catalan, N. et al. AID mutant analyses indicate requirement for class-switch-specific cofactors. Nat Immunol 4, 843–848 (2003). https://doi.org/10.1038/ni964

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