ACIDA gene

The ACIDA gene ACIDA is the acronym for "Activation Induced Cytidine Deaminase" and is loaclized on chromosome 12p13.31. The gene encodes an RNA-editing deaminase of the same name, which belongs to the cytidine deaminase (DNA deaminase) family and catalyzes the deamination of cytosine residues in single-stranded DNA (Muramatsu M et al. 1999).

AICDA is specifically expressed in germinal center-like B cells where it is enzymatically active. Although the activity of AID is essential for antibody diversification, it can be harmful to the organism under certain circumstances, as it can directly induce genomic instability and thus have a mutagenic effect.

Deaminase is involved in somatic hypermutation (SHM), gene conversion and class-switch recombination (CSR) in B lymphocytes. AICDA deaminates Ig variable (V) and Ig switch (S) region C to U DNA during transcription. Furthermore, ACIDA is required for several important steps of terminal B cell differentiation, which are essential for efficient antibody responses. It is also possible that deaminase plays a role in epigenetic regulation of gene expression by participating in DNA demethylation.

In principle, the expression of AID is restricted to stimulated B lymphocytes. However, it has been shown experimentally in animals that under certain circumstances Aicda can induce somatic hypermutations also in non-lymphoid cells (Okazaki et al. 2002).

Revy et al (2000) identified mutations in the AID gene in patients with the autosomal recessive form of hyper-IgM immunodeficiency syndrome type 2 (HIGM2; OMIM 605258; D80.5). The phenotype observed in patients with hyper-IgM syndrome indicates that AID is responsible for several crucial steps in terminal B-cell differentiation that are required for efficient antibody responses. Fagarasan et al. (2002) reported that deficiency of AID resulted in hyperplasia of isolated lymphoid follicles associated with a 100-fold increase in anaerobic flora in the small intestine. Antibiotic treatment in this animal experiment resulted in disappearance of hyperplasia of isolated lymphoid follicles and enlargement of germinal centers in secondary lymphoid tissues (Fagarasan S et al. 2002).

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