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Systematic name M8285
Brief description Genes down-regulated in peritoneal cavity B lymphocytes: wildtype versus lupus susceptibility locus Sle2c1.
Full description or abstract Sle2c1 is an NZM2410-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. Here we showed that expression of Sle2c1 enhances NZB cellular phenotypes that have been associated with autoimmune pathogenesis. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin kinase inhibitor p18INK4c (p18), as the top candidate gene for inducing the Slec2c1 associated expansion of B1a cells. A novel SNP in the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and B1a cells from Sle2c1-carrying mice, which leads to defective G1 cell cycle arrest in splenic B cells and increased proliferation of Pc B1a cells. As cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c play a critical role in B1a cell self renewal, and that its impaired expression leads to an accumulation of these cells with high autoreactive potential.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 21543644   Authors: Xu Z,Potula HH,Vallurupalli A,Perry D,Baker H,Croker BP,Dozmorov I,Morel L
Exact source GSE23114_3028_200_DN
Related gene sets (show 7 additional gene sets from the source publication)

(show 2 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform HUMAN_GENE_SYMBOL
Dataset references (show 1 datasets)
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Compendia expression profiles ? GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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