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Aiolos controls gene conversion and cell death in DT40 B cells.
1Turku Graduate School of Biomedical Sciences, University of Turku, Turku, Finland. elli.narvi@utu.fi
Scandinavian Journal of Immunology
|May 26, 2007
Summary
The transcription factor Aiolos is crucial for B cell survival and proper B-cell receptor gene diversification. Aiolos deficiency in B cells leads to increased apoptosis and impaired Ig gene conversion, suggesting a role beyond its known functions.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Aiolos, an Ikaros family transcription factor, is vital for B cell function.
- Aiolos-null mutant mice exhibit B cell activation, enhanced B-cell receptor (BCR) signaling, and lupus-like autoimmune disease.
- Aiolos's role in B cell apoptosis and somatic diversification remains unstudied.
Purpose of the Study:
- To investigate the role of Aiolos in B cell apoptosis.
- To determine if Aiolos regulates immunoglobulin (Ig) gene conversion in B cells.
- To elucidate the functional significance of Aiolos isoforms in B cell function.
Main Methods:
- Disruption of Aiolos in the DT40 B cell line.
- Induction of apoptosis via nutritional stress, BCR cross-linking, UV, and gamma irradiation.
- Analysis of Ig gene conversion and expression of activation-induced cytidine deaminase (AID).
- Re-expression of Aiolos isoforms (Aio-1 and Aio-2) in Aiolos-deficient cells.
Main Results:
- Aiolos-deficient B cells (Aiolos(-/-)) display increased sensitivity to apoptosis.
- Aiolos(-/-) cells exhibit defective Ig gene conversion, indicating impaired somatic diversification of the BCR repertoire.
- Re-expression of the DNA-binding isoform Aio-1 restored gene conversion, while the dominant-negative isoform Aio-2 did not.
- Reduced AID expression was observed in Aiolos(-/-) cells, but ectopic AID overexpression did not rescue the gene conversion defect.
Conclusions:
- Aiolos plays a critical role in preventing B cell apoptosis.
- Aiolos is essential for Ig gene conversion, a process vital for BCR repertoire diversification.
- Aiolos regulates gene conversion potentially independently of AID, highlighting the importance of alternative splicing within the Ikaros family.
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