Cyclin-dependent kinases regulate Ig class switching by controlling access of AID to the switch region

The Journal of Immunology : Official Journal of the American Association of Immunologists
Minghui HeEva Severinson

Abstract

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 G1 phase (<3.5 h), a total cell cycle time of ∼ 11 h, and that Ig class switching preferentially occurred in the late G1 or early S phase. Inhibition of cyclin-dependent 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 G1/S border.

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Citations

Feb 24, 2016·Nature Reviews. Immunology·Rafael CasellasJavier M Di Noia
Dec 30, 2015·Nature Genetics·Bernice Lo
Mar 14, 2019·Frontiers in Cell and Developmental Biology·Phatthamon Laphanuwat, Siwanon Jirawatnotai
Jan 27, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph N PucellaJayanta Chaudhuri
May 11, 2020·Seminars in Cell & Developmental Biology·Nathan Palmer, Philipp Kaldis

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