Activation-induced deaminase: controversies and open questions

Activation-induced deaminase (AID) is required for three distinct reactions crucial to the diversification of the antibody repertoire; these are somatic hypermutation (SHM), class switch recombination (CSR) and gene conversion (GC). AID is a cytidine deaminase and is believed to initiate these reactions by deaminating cytidine residues in single-stranded DNA in Ig genes. This reaction has the potential to produce DNA damage in non-Ig genes and to destabilize the genome. Here, we review the current understanding of how AID is targeted and mutates Ig genes and how genome integrity is maintained during SHM, CSR and GC.