somatic hypermutation

Pathology

• mistargetted somatic hypermutation may be involved in B-cell lymphomas

Biochemistry

Programmed process of mutation involving immunoglobulin variable regions that serves to diversify receptors of the immune system. Somatic hypermutation affects only individual cells. The mutations are not transmitted to offspring.

Somatic hypermutation occurs during B-cell proliferation. Mutation rate is 10E5-10E6 fold greater than normal rate of mutation. Most mutations are point mutations, with occasional deletions or insertions. The mutations occur largely at 'hotspots' in the immunoglobulin variable regions. This directed hypermutation allows for selection of B-cells that express immunoglobulin receptors with ability to recognize specific antigen.

Somatic hypermutation occurs largely (if not exclusively) via deamination of cytosine to uracil by activation-induced cytidine deaminase. The C-G base pair is thus directly mutated to a U-G mismatch. Rather than using high-fidelity DNA mismatch repair enzymes, uracil bases are remove by uracil-DNA-glycosylase & error-prone DNA polymerases are recruited to fill the gap & create mutations. Thus mutations may occur at the deaminated cytosine itself or neighboring base pairs.

More general terms

• mutation