Linked Life Data

17523942

Source:http://linkedlifedata.com/resource/pubmed/id/17523942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-25
pubmed:abstractText
The Ikaros family transcription factor Aiolos is important for B cell function, since B cells of Aiolos-null mutant mice exhibit an activated phenotype, enhanced B-cell receptor (BCR) signalling response and develop a systemic lupus erythematosus (SLE) type autoimmune disease. Aiolos has also been reported to interact with anti-apoptotic Bcl-2 and Bcl-x(L) in T cells, but whether Aiolos regulates cell death has not been studied in B cells. Here we show that the disruption of Aiolos in the DT40 B cell line induces a cell death sensitive phenotype, as the Aiolos(-/-) cells are more prone to apoptosis by nutritional stress, BCR cross-linking, UV- or gamma-irradiation. Furthermore, the Aiolos(-/-) cells have defective Ig gene conversion providing evidence that Aiolos is needed for the somatic diversification of the BCR repertoire. The re-expression of DNA-binding isoform Aio-1 was able to restore the gene conversion defect of the Aiolos-deficient cells, whereas the introduction of dominant negative isofom Aio-2 had no effect on gene conversion, thus demonstrating the functional importance of alternative splicing within Ikaros family. Although the Aiolos(-/-) cells exhibit reduced expression of activation-induced cytidine deaminase (AID), ectopic AID overexpression did not restore the gene conversion defect in the Aiolos(-/-) cells. Our findings indicate that Aiolos may regulate gene conversion in an AID independent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-9475
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
503-13
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Aiolos controls gene conversion and cell death in DT40 B cells.
pubmed:affiliation
Turku Graduate School of Biomedical Sciences, University of Turku, Turku, Finland. elli.narvi@utu.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't