Systematic name M1899
Brief description Gene down-regulated by CD40 [GeneID=958] signaling in Ramos cells (EBV negative Burkitt lymphoma).
Full description or abstract Substantial evidence indicates that signaling through the CD40 receptor (CD40) is required for germinal center (GC) and memory B-cell formation. However, it is not fully understood at which stages of B-cell development the CD40 pathway is activated in vivo. To address this question, we induced CD40 signaling in human transformed GC B cells in vitro and identified a CD40 gene expression signature by DNA microarray analysis. This signature was then investigated in the gene expression profiles of normal B cells and found in pre- and post-GC B cells (naive and memory) but, surprisingly, not in GC B cells. This finding was validated in lymphoid tissues by showing that the nuclear factor-kappaB (NF-kappaB) transcription factors, which translocate to the nucleus upon CD40 stimulation, are retained in the cytoplasm in most GC B cells, indicating the absence of CD40 signaling. Nevertheless, a subset of centrocytes and B cells in the subepithelium showed nuclear staining of multiple NF-kappaB subunits, suggesting that a fraction of naive and memory B cells may be subject to CD40 signaling or to other signals that activate NF-kappaB. Together, these results show that GC expansion occurs in the absence of CD40 signaling, which may act only in the initial and final stages of the GC reaction.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15331443   Authors: Basso K,Klein U,Niu H,Stolovitzky GA,Tu Y,Califano A,Cattoretti G,Dalla-Favera R
Exact source Table 1S: CD40 down-regulated genes
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(show 66 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform AFFY_HG_U95
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Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: Renamed from BASSO_GERMINAL_CENTER_CD40_DN

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