Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate.
Depending on the species and the lymphoid organ, activation-induced cytidine deaminase (AID) expression triggers diversification of the rearranged immunoglobulin (Ig) genes by pseudo V (psiV) gene- templated gene conversion or somatic hypermutation. To investigate how AID can alternatively induce recombination or hypermutation, psiV gene deletions were introduced into the rearranged light chain locus of the DT40 B-cell line. We show that the stepwise removal of the psiV donors not only reduces and eventually abolishes Ig gene conversion, but also activates AID-dependent Ig hypermutation. This strongly supports a model in which AID induces a common modification in the rearranged V(D)J segment, leading to a conversion tract in the presence of nearby donor sequences and to a point mutation in their absence.
Arakawa
Hiroshi
H
GSF-National Research Center for Environment and Health, Institute for Molecular Radiobiology, Neuherberg-Munich, Germany.
Saribasak
Huseyin
H
Buerstedde
Jean-Marie
JM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D003001:Cloning, Molecular; D003564:Cytidine Deaminase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005785:Gene Conversion; D017353:Gene Deletion; D007136:Immunoglobulins / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D045567:VDJ Recombinases / Q000378:metabolism
D007136:Immunoglobulins; D045567:VDJ Recombinases; D003564:Cytidine Deaminase