Document Detail


Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta.
MedLine Citation:
PMID:  11976687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.
Authors:
Akimoto Miyamoto; Keiko Nakayama; Hiroyuki Imaki; Sachiko Hirose; Yi Jiang; Masaaki Abe; Tadasuke Tsukiyama; Hiroyasu Nagahama; Shigeo Ohno; Shigetsugu Hatakeyama; Keiichi I Nakayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  416     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-26     Completed Date:  2002-05-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  865-9     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Autoantibodies / blood
Autoimmunity / immunology*
B-Lymphocytes / cytology*,  immunology*,  transplantation
CCAAT-Enhancer-Binding Protein-beta / metabolism
Cell Division
Flow Cytometry
Gene Deletion
Genes, RAG-1 / genetics
Glomerulonephritis / immunology,  pathology
Immune Tolerance / immunology
Immunoglobulin A / blood
Immunoglobulin G / blood
Interleukin-10 / genetics
Interleukin-6 / biosynthesis,  genetics
Isoenzymes / deficiency*,  genetics,  metabolism
Kidney / immunology,  pathology
Lymph Nodes / cytology,  immunology
Mice
Mice, Knockout
Protein Kinase C / deficiency*,  genetics,  metabolism
Protein Kinase C-delta
Spleen / cytology,  immunology
T-Lymphocytes / cytology,  immunology
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/CCAAT-Enhancer-Binding Protein-beta; 0/Immunoglobulin A; 0/Immunoglobulin G; 0/Interleukin-6; 0/Isoenzymes; 130068-27-8/Interleukin-10; EC 2.7.1.-/Prkcd protein, mouse; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-delta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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