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.
Bibliographical noteFunding Information:
R.S.H. is a fellow of the Natural Sciences and Engineering Research Council of Canada (NSERC). Our research on somatic hypermutation is supported by R01 GM41712 from the US National Institutes of Health.
- B cell
- DNA repair
- DNA replication
- Germinal center
- Mismatch repair
- Somatic hypermutation