title: Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase.
abstract: Thirteen Japanese patients with hyper-IgM syndrome but normal CD40 ligand were characterized. All patients had mutations in AID (activation-induced cytidine deaminase) gene. Five of them had a missense mutation of Arg112His. In all patients, serum IgG, IgA and IgE levels were undetectable, B cells failed to produce detectable amounts of IgE even if cultured them with anti-CD40 and IL-4. Somatic hypermutation (SHM) was also impaired in their peripheral blood B cells. These results suggest that Arg112 is the hot spot of AID mutation and demonstrate that AID plays indispensable roles in class switch recombination (CSR) and somatic hypermutation (SHM) in human B cells. In addition, serum IgM levels in the patients have been continuously high even after proper intravenous immunogloburin infusion (IVIG) and without infection, indicate that AID has the function to induce spontaneous IgM production in B cells.
authors.affiliation: Department of Human Ontogeny and Childhood Development, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D002675:Child, Preschool; D003241:Consanguinity; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D006942:Hypergammaglobulinemia / Q000201:enzymology* / Q000235:genetics*; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D007223:Infant; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D035781:Siblings; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013577:Syndrome
chemical_list: D007075:Immunoglobulin M; D023201:CD40 Ligand; D006639:Histidine; D001120:Arginine; D003564:Cytidine Deaminase