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Immunity. 2011 Feb 25;34(2):188-200. doi: 10.1016/j.immuni.2011.01.014. Epub 2011 Feb 17.

Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation.

Author information

  • 1McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705, USA.

Erratum in

  • Immunity. 2011 Mar 25;34(3):449.

Abstract

The N-terminal nuclear export sequence (NES) of inhibitor of nuclear factor kappa B (NF-κB) alpha (IκBα) promotes NF-κB export from the cell nucleus to the cytoplasm, but the physiological role of this export regulation remains unknown. Here we report the derivation and analysis of genetically targeted mice harboring a germline mutation in IκBα NES. Mature B cells in the mutant mice displayed nuclear accumulation of inactive IκBα complexes containing a NF-κB family member, cRel, causing their spatial separation from the cytoplasmic IκB kinase. This resulted in severe reductions in constitutive and canonical NF-κB activities, synthesis of p100 and RelB NF-κB members, noncanonical NF-κB activity, NF-κB target gene induction, and proliferation and survival responses in B cells. Consequently, mice displayed defective B cell maturation, antibody production, and formation of secondary lymphoid organs and tissues. Thus, IκBα nuclear export is essential to maintain constitutive, canonical, and noncanonical NF-κB activation potentials in mature B cells in vivo.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21333553
[PubMed - indexed for MEDLINE]
PMCID:
PMC3111750
Free PMC Article

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