Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytes.

Abstract

DNA breaks play an essential role in germinal centre B cells as intermediates to immunoglobulin class switching, a recombination process initiated by activation-induced cytidine deaminase (AID). Immunoglobulin gene hypermutation is likewise catalysed by AID but is believed to occur via single-strand DNA breaks. When improperly repaired, AID-mediated lesions can promote chromosomal translocations (CTs) that juxtapose the immunoglobulin loci to heterologous genomic sites, including oncogenes. Two of the most studied translocations are the t(8;14) and T(12;15), which deregulate cMyc in human Burkitt's lymphomas and mouse plasmacytomas, respectively. While a complete understanding of the aetiology of such translocations is lacking, recent studies using diverse mouse models have shed light on two important issues: (1) the extent to which non-specific or AID-mediated DNA lesions promote CTs, and (2) the safeguard mechanisms that B cells employ to prevent AID tumorigenic activity. Here we review these advances and discuss the usage of pristane-induced mouse plasmacytomas as a tool to investigate the origin of Igh-cMyc translocations and B-cell tumorigenesis.

• Authors: Rafael Casellas, Arito Yamane, Alexander L Kovalchuk, Michael Potter
• Journal: Immunology (Immunology) Vol. 126 Issue 3 Pg. 316-28 (Mar 2009) ISSN: 1365-2567 [Electronic] England
• PMID: 19302140 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Review)

Chemical References

• Cytidine Deaminase

Topics

• Animals
• B-Lymphocytes (enzymology, immunology)
• Cell Transformation, Neoplastic (genetics, immunology)
• Cytidine Deaminase (metabolism)
• Genes, Immunoglobulin Heavy Chain (immunology)
• Genes, myc (immunology)
• Lymphocyte Activation (immunology)
• Mice
• Plasmacytoma (genetics, immunology)
• Somatic Hypermutation, Immunoglobulin (immunology)
• Translocation, Genetic (immunology)