Precise dosage of an endogenous mutagen in the immune system.
Four decades ago, it was hypothesized that lymphocytes mutate the immunoglobulin loci at a rate much greater than the spontaneous rate. Over time this Ig somatic hypermutation became the prime example of in vivo, site-directed mutagenesis. But recent studies have demonstrated that this is not necessarily the case, and that hypermutation occurs not only at the Ig locus but also at various locations throughout the genome. Here, we propose that hypermutation can be genome-wide with minimal injury, if a sufficient mutation rate is coupled with strong clonal selection.
Wang
Clifford L
CL
Department of Microbiology and Immunology, University of California, San Francisco, California 94143-0414, USA. diffw@itsa.ucsf.edu
Wabl
Matthias
M
D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics; D018628:Gene Dosage; D007107:Immune System / Q000737:chemistry* / Q000378:metabolism*; D016296:Mutagenesis / Q000235:genetics*; D009153:Mutagens / Q000737:chemistry* / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D009153:Mutagens; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase