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Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Induction and Assessment of Class Switch Recombination in Purified Murine B Cells

Published on: August 13, 2010

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

Minghui He1, Elena M Cortizas2, Ramiro E Verdun3

  • 1Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden;

Journal of Immunology (Baltimore, Md. : 1950)
|March 22, 2015
PubMed

Insights

Immunoglobulin class switching is linked to cell division and proliferation. This study reveals cyclin-dependent kinase 2 (CDK2) regulates nuclear access of activation-induced cytidine deaminase (AID), influencing immunoglobulin class switching.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Immunoglobulin (Ig) class switching is a crucial adaptive immune process that requires B cell proliferation and is linked to cell division.
  • The precise molecular mechanisms underlying this division-linked Ig class switching remain largely unknown.

Purpose of the Study:

  • To elucidate the cell cycle regulation and molecular mechanisms governing Ig class switching.
  • To investigate the role of cell cycle regulators, specifically cyclin-dependent kinases (CDKs), in the targeting of activation-induced cytidine deaminase (AID) during Ig class switching.

Main Methods:

  • Kinetic analysis of early switching B cells to determine cell cycle phase durations and timing of Ig class switching.
  • Inhibition of CDKs to assess their impact on the switching rate and AID targeting.
  • Ectopic expression of nuclear AID in HeLa cells to study its cell cycle-dependent localization.
  • Analysis of AID nuclear accumulation in CDK2 hypomorphic cells.

Main Results:

  • Proliferating B cells exhibit a short G1 phase (<3.5 h) and a total cell cycle time of approximately 11 hours.
  • Ig class switching preferentially occurs during the late G1 or early S phase of the cell cycle.
  • CDK inhibition significantly reduces the Ig class switching rate by impairing AID targeting to the Igh locus.
  • Nuclear AID localization in HeLa cells is preferentially observed during the early S phase.
  • CDK2 deficiency leads to reduced nuclear accumulation of AID.

Conclusions:

  • Division-linked Ig class switching is partially regulated by CDK2-mediated control of AID nuclear access at the G1/S phase border.
  • These findings provide a mechanistic link between B cell proliferation, cell cycle progression, and the efficiency of Ig class switching.

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