AID mediates innate immunity to endogenous retroelements

A member of the APOBEC protein family, activation-induced cytidine deaminase (AID) is a B-cell-specific mutator that deaminates cytosine to uracil in DNA. AID mediates somatic hypermutation and class switch recombination of immunoglobulin genes—processes important for the generation of high-affinity antibodies and changes in antibody effector functions, respectively. Recent data, including our own, suggest that AID may not only function in adaptive, but also in innate immunity. AID may inhibit retroelements—a function that is well established for APOBEC3 proteins. If unrestricted, endogenous retroelements accumulate in the cytoplasm and insert their DNA into the host genome, with the potential to cause disease ranging from cancer to autoimmunity. We found that AID inhibits the retrotransposition of LINE-1 (L1) retroelements in vitro. In activated B cells, AID forms cytoplasmic high molecular mass complexes with L1 mRNA and decreases the protein level of open reading frame 1 (ORF1) of L1 elements. We propose that AID protects B cells from the adverse effects of retroelements, such as insertional mutagenesis.