期刊
IMMUNOLOGY
卷 126, 期 3, 页码 316-328出版社
WILEY
DOI: 10.1111/j.1365-2567.2008.03050.x
关键词
activation-induced cytidine deaminase; chromosomal translocations; class switch recombination; somatic hypermutation; tumorigenesis
类别
资金
- Intramural Research Program of NIAMS
- NCI of the National Institutes of Health
- NATIONAL CANCER INSTITUTE [ZIABC005596, Z01BC005596] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZICAR041186, ZIAAR041149, ZIAAR041148, Z01AR041148, Z01AR041149] Funding Source: NIH RePORTER
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.
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