Document Detail


Cyclin-dependent kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1.
MedLine Citation:
PMID:  21543644     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sle2c1 is an NZM2410- and NZB-derived lupus susceptibility locus that induces an expansion of the B1a cell compartment. B1a cells have a repertoire enriched for autoreactivity, and an expansion of this B cell subset occurs in several mouse models of lupus. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18(INK4c) (p18), as the top candidate gene for inducing the Slec2c1-associated expansion of B1a cells. A novel single nucleotide polymorphism in the NZB allele of the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and peritoneal cavity B1a cells from Sle2c1-carrying mice, which leads to a defective G1 cell cycle arrest in splenic B cells and increased proliferation of peritoneal cavity B1a cells. As the cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c plays a critical role in B1a cell self-renewal and that its impaired expression leads to an accumulation of these cells with high autoreactive potential.
Authors:
Zhiwei Xu; Hari-Hara S K Potula; Anusha Vallurupalli; Daniel Perry; Henry Baker; Byron P Croker; Igor Dozmorov; Laurence Morel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-04
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-07     Completed Date:  2011-10-07     Revised Date:  2013-09-20    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6673-82     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoimmunity / genetics
B-Lymphocyte Subsets / pathology
B-Lymphocytes / cytology,  pathology*,  physiology
Cell Cycle
Cell Proliferation
Chromosome Mapping
Cyclin-Dependent Kinase Inhibitor p18 / genetics,  physiology*
Disease Models, Animal
Genetic Loci / genetics
Genetic Predisposition to Disease / genetics*
Homeostasis*
Lupus Erythematosus, Systemic / genetics,  pathology*
Lymphocyte Count
Mice
Polymorphism, Single Nucleotide
Grant Support
ID/Acronym/Agency:
K01 AR056725/AR/NIAMS NIH HHS; K01AR056725/AR/NIAMS NIH HHS; P30 AR053483/AR/NIAMS NIH HHS; R01 AI068965/AI/NIAID NIH HHS; R01 AI068965/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cdkn2c protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p18
Comments/Corrections

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