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Science 15 November 2002:
Vol. 298. no. 5597, pp. 1424 - 1427
DOI: 10.1126/science.1077336
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Reports

Critical Roles of Activation-Induced Cytidine Deaminase in the Homeostasis of Gut Flora

Sidonia Fagarasan,12* Masamichi Muramatsu,1* Keiichiro Suzuki,1 Hitoshi Nagaoka,1 Hiroshi Hiai,3 Tasuku Honjo1dagger

Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID-/- mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora.

1 Department of Medical Chemistry,
3 Department of Pathology and Biology of Disease, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
2 RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: honjo{at}mfour.med.kyoto-u.ac.jp

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