Genome-wide somatic hypermutation.

DNA mutagenesis is generally considered harmful. Yet activated B cells normally mutate the Ig loci. Because this somatic hypermutation is potentially dangerous, it has been hypothesized that mutations do not occur throughout the genome but instead are actively targeted to the Ig loci. Here we challenge this longstanding and widely accepted hypothesis. We demonstrate that hypermutation requires no Ig gene sequences. Instead, activation-induced cytidine deaminase and other trans-acting hypermutation factors may function as general mutators.