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

Cell. 2000 Sep 1;102(5):565-75. doi: 10.1016/s0092-8674(00)00079-9.

Abstract

The activation-induced cytidine deaminase (AID) gene, specifically expressed 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 patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-1 Deaminase
  • Adolescent
  • Amino Acid Sequence
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Division
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 12 / genetics
  • Cloning, Molecular
  • Cytidine Deaminase / chemistry
  • Cytidine Deaminase / deficiency*
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / metabolism*
  • DNA Mutational Analysis
  • Female
  • Gene Deletion
  • Genes, Recessive / genetics*
  • Germinal Center / immunology
  • Germinal Center / pathology
  • Humans
  • Hyperplasia / genetics
  • Hyperplasia / pathology
  • Hyperplasia / physiopathology
  • Immunoglobulin M / genetics*
  • Immunoglobulin M / immunology
  • Immunologic Deficiency Syndromes / enzymology*
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Infant
  • Lod Score
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphocyte Activation
  • Male
  • Molecular Sequence Data
  • Palatine Tonsil / immunology
  • Palatine Tonsil / pathology
  • Pedigree
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics

Substances

  • Immunoglobulin M
  • RNA, Messenger
  • AICDA (activation-induced cytidine deaminase)
  • APOBEC-1 Deaminase
  • APOBEC1 protein, human
  • Apobec1 protein, mouse
  • Cytidine Deaminase

Associated data

  • GENBANK/AB040430
  • GENBANK/AB040431