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.
Original language | English (US) |
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Pages (from-to) | 316-328 |
Number of pages | 13 |
Journal | Immunology |
Volume | 126 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2009 |
Externally published | Yes |
Keywords
- Activation-induced cytidine deaminase
- Chromosomal translocations
- Class switch recombination
- Somatic hypermutation
- Tumorigenesis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology