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Cyclin-Dependent Kinases Regulate Ig Class Switching by Controlling Access of AID to the Switch Region
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Number of Authors: 4
2015 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 194, no 9, 4231-4239 p.Article in journal (Refereed) Published
Abstract [en]

Ig class switching requires cell proliferation and is division linked, but the detailed mechanism is unknown. By analyzing the first switching cells early in the kinetics, our analysis suggested that proliferating B cells had a very short G(1) phase (<3.5 h), a total cell cycle time of similar to 11 h, and that Ig class switching preferentially occurred in the late G(1) or early S phase. Inhibition of cyclindependent kinases (CDKs) caused dramatic reduction of switching rate within 6 h. This was associated with less targeting of activation-induced cytidine deaminase (AID) to the Igh locus. Interestingly, ectopically expressed nuclear AID in HeLa cells was preferentially found in the early S phase. Furthermore, in CDK2 hypomorphic cells there was reduced nuclear AID accumulation. Thus, our data are compatible with the idea that division-linked Ig class switching is in part due to CDK2-regulated AID nuclear access at the G(1)/S border.

Place, publisher, year, edition, pages
2015. Vol. 194, no 9, 4231-4239 p.
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:su:diva-117786DOI: 10.4049/jimmunol.1402146ISI: 000353727400022OAI: oai:DiVA.org:su-117786DiVA: diva2:816194
Available from: 2015-06-02 Created: 2015-06-01 Last updated: 2017-12-04Bibliographically approved

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