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Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation. Immunity 2011 Feb 25;34(2):188-200

Date

02/22/2011

Pubmed ID

21333553

Pubmed Central ID

PMC3111750

DOI

10.1016/j.immuni.2011.01.014

Scopus ID

2-s2.0-79951768852   14 Citations

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.

Author List

Wuerzberger-Davis SM, Chen Y, Yang DT, Kearns JD, Bates PW, Lynch C, Ladell NC, Yu M, Podd A, Zeng H, Huang TT, Wen R, Hoffmann A, Wang D, Miyamoto S

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Active Transport, Cell Nucleus
Animals
B-Lymphocytes
Cell Death
Cell Division
Gene Expression Regulation
Germ-Line Mutation
I-kappa B Kinase
I-kappa B Proteins
Immunologic Deficiency Syndromes
Lymph Nodes
Lymphoid Tissue
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
NF-KappaB Inhibitor alpha
NF-kappa B
Nuclear Export Signals
Organ Size
Peyer's Patches
Proto-Oncogene Proteins c-rel
Spleen
Transcription, Genetic
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5