Activation‐induced cytidine deaminase (AID) is expressed in normal spermatogenesis but only infrequently in testicular germ cell tumours

Abstract

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes in antigen-dependent B-cell maturation. SHM is not restricted to immunoglobulin gene loci, raising the possibility of a function for AID in other cell types. In this study, it is shown that AID is expressed in spermatocytes in the human testis. AID was mostly cytoplasmic but nuclear AID was also observed in a proportion of cells, in keeping with the DNA deamination model of AID function. Intratubular germ cell neoplasia unclassified (IGCNU), the precursor lesion of testicular cancers, was AID-negative. Seminomas also lacked AID expression. Nuclear and cytoplasmic AID expression was observed in three of 32 mixed non-seminomatous germ cell tumours. The results provide evidence for a physiological role for AID outside the immune system. AID expression in spermatocytes points to a role in meiosis. It remains uncertain whether AID may also contribute to the genetic aberrations characteristically found in testicular germ cell tumours. The consistent absence of detectable AID expression in atypical spermatogonia of IGCNU and its rare expression in germ cell tumours suggest that continued expression of AID is not involved in the pathogenesis of germ cell tumours.

A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations

“…We reported earlier the lack of lymphomagenesis in B-cellspecific AID transgenic mice obtained by crossing the same AID cTg line with CD19-Cre mice (Muto et al, 2006), suggesting that some protective mechanism might exist in B cells, which have physiological expression of AID. A similar reason might apply to germ cells because AID has been reported to be expressed physiologically in the human testis (Schreck et al, 2006) and mouse ovary (Morgan et al, 2004).…”

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: Background to spermatogenesis, spermatogonia, and spermatocytes

“…Mouse meiosis-related protein 2 [ID: T1-173], a 28.4 kDa protein, is present in secondary mouse spermatocytes (Gu et al, 2005). Activation-induced cytidine deaminase [ID: T1-174] is expressed in human spermatocytes where it may play a role in meiosis possibly with an involvement in DNA deamination (Schreck et al, 2006). Testisin [ID: T1-175] is a cell surface-anchored serine proteinase expressed in primary spermatocytes with three known isoforms being generated by alternate premRNA splicing (Hooper et al, 2000).…”

Activation-induced cytidine deaminase (AID) is necessary for the epithelial–mesenchymal transition in mammary epithelial cells

“…However, AID is also expressed at much lower levels during B-cell development, where it mediates B-cell tolerance by an as yet undefined mechanism (4,5). In addition, AID is present at low levels in pluripotent cells such as oocytes, embryonic germ cells, embryonic stem cells (6), and spermatocytes (7), where it may have a function beyond antibody gene diversification (8)(9)(10). AID expression is induced by inflammatory paracrine signals such as interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), and transforming growth factor beta (TGFβ) (11)(12)(13), and it has been detected in multiple epithelial tissues in association with chronic inflammatory conditions that promote tumorigenesis (14)(15)(16)(17)(18).…”