Type Two Hyper-IgM Syndrome caused by Mutation in Activation-Induced Cytidine Deaminase

Thirteen Japanese patients with hyper-IgM syndromebut normal CD40 ligand were characterized.All patients had mutations in AID (activationinducedcytidine deaminase) gene. Five of themhad a missense mutation of Arg112His. In allpatients, serum IgG, IgA and IgE levels wereundetectable, B cells failed to produce detectableamounts of IgE even if cultured them with anti-CD40 and IL-4. Somatic hypermutation (SHM) wasalso impaired in their peripheral blood B cells.These results suggest that Arg112 is the hot spot ofAID mutation and demonstrate that AID playsindispensable roles in class switch recombination(CSR) and somatic hypermutation (SHM) inhuman B cells. In addition, serum IgM levels in thepatients have been continuously high even afterproper intravenous immunogloburin infusion(IVIG) and without infection, indicate that AID hasthe function to induce spontaneous IgM productionin B cells.