Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate |
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Authors: | Arakawa Hiroshi Saribasak Huseyin Buerstedde Jean-Marie |
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Institution: | 1
GSF–National Research Center for Environment and Health, Institute for Molecular Radiobiology, Neuherberg-Munich
Germany |
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Abstract: | 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 (ψV) gene- templated gene conversion or somatic hypermutation. To investigate how AID can alternatively induce recombination or hypermutation, ψV gene deletions were introduced into the rearranged light chain locus of the DT40 B-cell line. We show that the stepwise removal of the ψV 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. |
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