title: Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer.
abstract: Activation-induced cytidine deaminase (AID) is critically involved in class switch recombination and somatic hypermutation of Ig loci resulting in diversification of antibodies repertoire and production of high-affinity antibodies and as such represents a physiological tool to introduce DNA alterations. These processes take place within germinal centers of secondary lymphoid organs. Under physiological conditions, AID is expressed predominantly in activated B lymphocytes. Because of the mutagenic and recombinogenic potential of AID, its expression and activity is tightly regulated on different levels to minimize the risk of unwanted DNA damage. However, chronic inflammation and, probably, combination of other not-yet-identified factors are able to create a microenvironment sufficient for triggering an aberrant AID expression in B cells and, importantly, in non-B-cell background. Under these circumstances, AID may target also non-Ig genes, including cancer-related genes as oncogenes, tumor suppressor genes, and genomic stability genes, and modulate both genetic and epigenetic information. Despite ongoing progress, the complete understanding of fundamental aspects is still lacking as (1) what are the crucial factors triggering an aberrant AID expression/activity including the impact of Th2-driven inflammation and (2) to what extent may aberrant AID in human non-B cells lead to abnormal cell state associated with an increased rate of genomic alterations as point mutations, small insertions or deletions, and/or recurrent chromosomal translocations during solid tumor development and progression.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. diana.mechtcheriakova@meduniwien.ac.at
authors.forename: Diana
authors.initials: D
authors.lastname: Mechtcheriakova
authors.forename: Martin
authors.initials: M
authors.lastname: Svoboda
authors.forename: Anastasia
authors.initials: A
authors.lastname: Meshcheryakova
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*
chemical_list: D003564:Cytidine Deaminase