Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora.
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.
Fagarasan
Sidonia
S
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Muramatsu
Masamichi
M
Suzuki
Keiichiro
K
Nagaoka
Hitoshi
H
Hiai
Hiroshi
H
Honjo
Tasuku
T
D000818:Animals; D000900:Anti-Bacterial Agents; D001402:B-Lymphocytes / Q000276:immunology; D001420:Bacteria, Aerobic / Q000254:growth & development*; D001421:Bacteria, Anaerobic / Q000254:growth & development*; D002455:Cell Division; D015169:Colony Count, Microbial; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000276:immunology; D004359:Drug Therapy, Combination / Q000494:pharmacology; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000276:immunology; D006706:Homeostasis; D006965:Hyperplasia; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010581:Peyer's Patches / Q000473:pathology; D027041:Somatic Hypermutation, Immunoglobulin; D013601:T-Lymphocytes / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000900:Anti-Bacterial Agents; D007135:Immunoglobulin Variable Region; D008795:Metronidazole; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase