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PMID: 11181694 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

IkappaB kinase alpha is essential for mature B cell development and function.

The Journal of experimental medicine ·Vol. 193 ·No. 4 ·2001-02-19 ·Pages 417-26

Kaisho T, Takeda K, Tsujimura T, Kawai T, Nomura F, Terada N, Akira S

Abstract

IkappaB kinase (IKK) alpha and beta phosphorylate IkappaB proteins and activate the transcription factor, nuclear factor (NF)-kappaB. Although both are highly homologous kinases, gene targeting experiments revealed their differential roles in vivo. IKKalpha is involved in skin and limb morphogenesis, whereas IKKbeta is essential for cytokine signaling. To elucidate in vivo roles of IKKalpha in hematopoietic cells, we have generated bone marrow chimeras by transferring control and IKKalpha-deficient fetal liver cells. The mature B cell population was decreased in IKKalpha(-/-) chimeras. IKKalpha(-/-) chimeras also exhibited a decrease of serum immunoglobulin basal level and impaired antigen-specific immune responses. Histologically, they also manifested marked disruption of germinal center formation and splenic microarchitectures that depend on mature B cells. IKKalpha(-/-) B cells not only showed impairment of survival and mitogenic responses in vitro, accompanied by decreased, although inducible, NF-kappaB activity, but also increased turnover rate in vivo. In addition, transgene expression of bcl-2 could only partially rescue impaired B cell development in IKKalpha(-/-) chimeras. Taken together, these results demonstrate that IKKalpha is critically involved in the prevention of cell death and functional development of mature B cells.

MeSH Terms
Animals B-Lymphocytes/cytology,immunology Bone Marrow Cells Cell Differentiation DNA-Binding Proteins/genetics,metabolism Germinal Center I-kappa B Proteins Lymphocyte Count Mice Mice, Mutant Strains NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors Spleen Transplantation Chimera Transplants
Chemicals
DNA-Binding Proteins I-kappa B Proteins NF-kappa B Nfkbia protein, mouse NF-KappaB Inhibitor alpha
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kaisho T
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Takeda K
Tsujimura T
Kawai T
Nomura F
Terada N
Akira S
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.193.4.417
Published
2001-02-19
Pages
417-26
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195900
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.193.4.417 PMC Full Text View journal details
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