The regulation of somatic hypermutation

Somatic hypermutation and class switch recombination cause genetic alterations in immunoglobulin (lg) genes, which underlie the generation of the secondary antibody repertoire in B lymphocytes. Both processes require activation-induced cytidine deaminase (AID), whose mechanism of action in not yet known in detail, but which mediates the accumulation of point mutations in the lg locus. This highly mutagenic process must be tightly controlled, and multiple levels of regulation might exist. Recent experiments show that AID deaminates deoxycytidine to deoxyuridine in single-stranded DNA. This mutagenic event is targeted to actively transcribed sequences, and the specificity of deamination might be related to the chromatin structure of the transcription complex.