In a phosphorylation-dependent positive feedback loop, the cytidine deaminase AID amplifies the generation of double-strand DNA breaks, which shows it can also function downstream of deamination. Antibody diversification in B lymphocytes, through the combined processes of variable-(diversity)-joining recombination, somatic hypermutation (SHM) and class-switch recombination (CSR), is necessary to produce an arsenal of antibodies with wide-ranging specificities and effector functions to mount a response to an almost infinite repertoire of antigens. Both SHM and CSR rely entirely on the cytidine deaminase AID to generate deoxycytidine-to-deoxyuridine (C-to-U) mutations in the variable (V) region of the immunoglobulin gene during SHM and in the constant (C) region of the immunoglobulin heavy-chain locus (Igh) during CSR.
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