Regulation of activation-induced cytidine deaminase DNA deamination activity in B-cells by Ser38 phosphorylation

Human and mouse Ig genes are diversified in mature B-cells by distinct processes known as Ig heavy-chain CSR (class switch recombination) and Ig variable-region exon SHM (somatic hypermutation). These DNA-modification processes are initiated by AID (activation-induced cytidine deaminase), a DNA cytidine deaminase predominantly expressed in activated B-cells. AID is post-transcriptionally regulated via multiple mechanisms, including microRNA regulation, nucleocytoplasmic shuttling, ubiquitination and phosphorylation. Among these regulatory processes, AID phosphorylation at Ser(38) has been a focus of particularly intense study and debate. In the present paper, we discuss recent biochemical and mouse genetic studies that begin to elucidate the functional significance of AID Ser(38) phosphorylation in the context of the evolution of this mode of AID regulation and the potential roles that it may play in activated B-cells during a normal immune response.