Activation-Induced Cytidine Deaminase (AID) is a crucial enzyme in the adaptive immune system, primarily involved in the diversification of antibodies. It is a member of the APOBEC (Apolipoprotein B mRNA Editing Catalytic Polypeptide-like) family of RNA/DNA editing enzymes . AID is encoded by the AICDA gene in humans and is known for its ability to deaminate cytosine residues in DNA, converting them into uracil .
AID plays a pivotal role in two key processes in B lymphocytes: somatic hypermutation (SHM) and class switch recombination (CSR) . These processes are essential for the generation of high-affinity antibodies and the diversification of the antibody repertoire. SHM introduces point mutations in the variable regions of immunoglobulin genes, enhancing the affinity of antibodies for their antigens. CSR, on the other hand, changes the constant region of the antibody, altering its effector function without affecting its antigen specificity .
The primary function of AID is to deaminate cytidine to uracil in single-stranded DNA. This deamination is a critical step in SHM and CSR. The uracil residues introduced by AID are recognized as thymine by the DNA repair machinery, leading to mutations . In SHM, these mutations occur in the variable regions of immunoglobulin genes, while in CSR, they occur in the switch regions of the immunoglobulin heavy chain locus .
AID activity is tightly regulated at multiple levels to prevent unwanted mutations that could lead to genomic instability and cancer . Dysregulation of AID can result in increased mutation load, chromosomal translocations, and disturbed genomic integrity, contributing to the development of lymphomas and other cancers . Chronic inflammation and other adverse cellular conditions can lead to the overexpression of AID, further increasing the risk of malignancies .
Human recombinant AID is produced using recombinant DNA technology, which involves cloning the AICDA gene into an expression vector and introducing it into a suitable host cell for protein production. This recombinant enzyme is used in various research applications to study its role in antibody diversification, DNA demethylation, and its implications in cancer and autoimmune diseases .
AID has been implicated in several diseases beyond its role in the immune system. Its ability to induce mutations and epigenetic changes makes it a significant player in the development of both lymphoid and non-lymphoid cancers . Additionally, AID’s role in active DNA demethylation has potential implications in epigenetic therapies .