Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Down-regulation of BLIMP1-alpha by the EBV oncogene, LMP1, disrupts the plasma cell differentiation program and prevents viral replication in B cells

ABSTRACT: In this study, we have investigated the effect of BLIMP1α on gene expression, cell differentiation and pathogenesis in normal human GC B cells using a non-viral vector based system Gene expression was compared among BLIMP1α, LMP1-transfected and control vector-transfected GC B cells from two patients. RNA from the FACS-sorted transfected GC B cells was amplified. Fragmented cRNA was hybridized to HG-U133 Plus 2.0 microarrays. Differentially expressed genes were identified using the GCOS pair-wise analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Wenbin Wei

PROVIDER: E-GEOD-27670 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas.

Vrzalikova Katerina K Vockerodt Martina M Leonard Sarah S Bell Andrew A Wei Wenbin W Schrader Alexandra A Wright Kenneth L KL Kube Dieter D Rowe Martin M Woodman Ciaran B CB Murray Paul G PG

Blood 20110316 22

An important pathogenic event in Epstein-Barr virus (EBV)-associated lymphomas is the suppression of virus replication, which would otherwise lead to cell death. Because virus replication in B cells is intimately linked to their differentiation toward plasma cells, we asked whether the physiologic signals that drive normal B-cell differentiation are absent in EBV-transformed cells. We focused on BLIMP1α, a transcription factor that is required for plasma cell differentiation and that is inactiva ...[more]

PMID: 21411757

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Project description:The goal of the study was to identify the genes which are regulated by Interleukin-2 in the CD4+ T cells of the scurfy mice during regulatory T-cell deficiency. Scurfy (Sf) mice bear a mutation in the forkhead box P3 (Foxp3) transcription factor, lack regulatory T-cells (Treg), develop multi-organ inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. Sf mice lacking the Il2 gene (Sf.Il2-/-), despite devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver, pancreas, submandibular gland and colon remained. Genome-wide microarray analysis revealed hundreds of genes were differentially regulated among Sf, Sf.Il2-/-, and B6 CD4+ T-cells but the most changes were those encoding receptors for trafficking/chemotaxis/retention and lymphokines. Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice in an apparent "organ-specific" manner through two novel mechanisms: by regulating the expression of genes encoding receptors for T-cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and lymphokine production. Thus, IL-2 is a master regulator for multi-organ inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation. Methods: CD4+ T cells were purified by Fluorescence Assisted Cell Sorting from the peripheral lymph nodes of (A) three individual Scurfy (Sf; B6.Cg-Foxp3sf/J) male mice, (B) three individual Sf.Il2-/- male mice (Scurfy mice carrying a null Interleukin (IL)-2 gene (B6.129P2-Il2tm1Hor/J)) and (C) a pooled sample of lymph nodes from two B6 (C57BL/6J) mice. All the mice were 3 weeks old. Total RNA was prepared using RNeasy mini kit (Qiagen). RNA samples were converted to cRNA, labeled and hybridized to Affymetrix Mouse 430_2 chips (Mouse Genome 430 2.0 Array, Affymetrix, Santa Clara, CA) at the University of Virginia DNA Sciences Core Facility. 1. RNA from CD4+ T cells purified from pooled peripheral lymph nodes of two 3-week old B6 mice) - 1 biological replicate 2. RNA from CD4+ T-cells purified from peripheral lymph nodes of 3-week old scurfy (Sf) mice - 3 biological replicates. 3. RNA from CD4+ T cells purified from peripheral lymph nodes of Sf.Il2-/- mice - 3 biological replicates.

Dataset Information

Down-regulation of BLIMP1-alpha by the EBV oncogene, LMP1, disrupts the plasma cell differentiation program and prevents viral replication in B cells

Publications

Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas.

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