The activation-induced deaminase functions in a postcleavage step of the somatic hypermutation process.
Activation of B cells by antigen fuels two distinct molecular modifications of immunoglobulin (Ig) genes. Class-switch recombination (CSR) replaces the Ig(mu) heavy chain constant region with a downstream constant region gene, thereby altering the effector function of the resulting antibodies. Somatic hypermutation (SHM) introduces point mutations into the variable regions of Ig genes, thereby changing the affinity of antibody for antigen. Mechanistic overlap between the two reactions has been suggested by the finding that both require the activation-induced cytidine deaminase (AID). It has been proposed that AID initiates both CSR and SHM by activating a common nuclease. Here we provide evidence that cells lacking AID, or expressing a dominant negative form of the protein, are still able to incur DNA lesions in SHM target sequences. The results indicate that an intact cytidine deaminase motif is required for AID function, and that AID acts downstream of the initial DNA lesions in SHM.
Papavasiliou
F Nina
FN
Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021, USA. papavasiliou@rockefeller.edu
Schatz
David G
DG
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007127:Immunoglobulin Constant Regions; D007148:Immunoglobulin mu-Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase