Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2)

The activation-induced cytidine deaminase (AID) gene, specifically expresse d in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in pati ents with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immuno globulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of g iant germinal centers. The phenotype observed in HIGM2 patients (and in AID (-/-) mice) demonstrates the absolute requirement for AID in several crucia l steps of B cell terminal differentiation necessary for efficient antibody responses.