Somatic hypermutation and the three R's: repair, replication and recombination.
Somatic hypermutation introduces single base changes into the rearranged variable (V) regions of antigen activated B cells at a rate of approximately 1 mutation per kilobase per generation. This is nearly a million-fold higher than the typical mutation rate in a mammalian somatic cell. Rampant mutation at this level could have a devastating effect, but somatic hypermutation is accurately targeted and tightly regulated. Here, we provide an overview of immunoglobulin gene somatic hypermutation; discuss mechanisms of mutation in model organisms that may be relevant to the hypermutation mechanism; and review recent advances toward understanding the possible role(s) of DNA repair, replication, and recombination in this fascinating process.
Harris
R S
RS
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, New Haven, CT 06520-8114, USA.
Kong
Q
Q
Maizels
N
N
D000818:Animals; D000940:Antigenic Variation; D001402:B-Lymphocytes / Q000276:immunology; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics