Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense.
To elucidate the specific role of somatic hypermutation (SHM) in mucosal immunity, we generated mice carrying a knock-in point mutation in Aicda, which encodes activation-induced cytidine deaminase (AID), an enzyme essential to SHM and class-switch recombination (CSR). These mutant AID(G23S) mice had much less SHM but had normal amounts of immunoglobulin in both serum and intestinal secretions. AID(G23S) mice developed hyperplasia of germinal center B cells in gut-associated lymphoid tissues, accompanied by expansion of microflora in the small intestine. Moreover, AID(G23S) mice had more translocation of Yersinia enterocolitica into mesenteric lymph nodes and were more susceptible than wild-type mice to oral challenge with cholera toxin. Together our results indicate that SHM is critical in maintaining intestinal homeostasis and efficient mucosal defense.
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Min
M
Wei
Reiko
R
Shinkura
Yasuko
Y
Doi
Mikako
M
Maruya
Sidonia
S
Fagarasan
Tasuku
T
Honjo
D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology*; D055879:Gene Knock-In Techniques; D005838:Genotype; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D051379:Mice; D009154:Mutation; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
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