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
02/22/2011Pubmed ID
21333553Pubmed Central ID
PMC3111750DOI
10.1016/j.immuni.2011.01.014Scopus ID
2-s2.0-79951768852 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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 SAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Active Transport, Cell NucleusAnimals
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
