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

Minghui He, Elena M. Cortizas, Ramiro E. Verdun, Eva Severinson

Research output: Contribution to journalArticle

8 Scopus citations

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 G 1 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.

Original languageEnglish (US)
Pages (from-to)4231-4239
Number of pages9
JournalJournal of Immunology
Volume194
Issue number9
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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