Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

LMP2A mediated gene expression changes in transfected CD10+ GCB cells

ABSTRACT: In this study, we have investigated the effect of LMP2A on gene expression in normal human GC B cells using a non-viral vector based system Keywords: transfection of viral oncogene in normal human B cells Gene expression was compared between LMP2A-transfected and control vector-transfected GC B cells from three patients. RNA from the FACS-sorted transfected GC B cells was amplified. 10ug of fragmented cRNA was hybridized to HG-U133 Plus 2.0 microarrays. Differentially expressed probe sets were identified using limma with a fold change >1.3 and p < 0.01

ORGANISM(S): Homo sapiens

SUBMITTER: Wenbin Wei

PROVIDER: E-GEOD-46143 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle.

Vockerodt Martina M Wei Wenbin W Nagy Eszter E Prouzova Zuzana Z Schrader Alexandra A Kube Dieter D Rowe Martin M Woodman Ciaran B CB Murray Paul G PG

The Journal of pathology 20130801 4

Hodgkin's lymphoma is unusual among B cell lymphomas, in so far as the malignant Hodgkin/Reed-Sternberg (HRS) cells lack a functional B cell receptor (BCR), as well as many of the required downstream signalling components. In Epstein-Barr virus (EBV)-positive cases of Hodgkin's lymphoma, HRS cells express the viral latent membrane proteins (LMP)-1 and -2A. LMP2A is thought to contribute to the pathogenesis of Hodgkin's lymphoma by providing a surrogate BCR-like survival signal. However, LMP2A ha ...[more]

PMID: 23592216

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Project description:Abstract: Epstein-Barr virus (EBV) infects germinal center (GC) B cells and establishes persistent infection in memory B cells. EBV-infected B cells sometimes cause B cell malignancies in humans with T- or NK-cell deficiency. We now find EBV-encoded Latent Membrane Protein 2A (LMP2A) to mimic B cell antigen receptor (BCR) signaling in murine GC B cells, causing altered humoral immune responses and autoimmune diseases. Investigation of the impact of LMP2A on B cell differentiation in mice that conditionally express LMP2A in GC B cells, or all B-lineage cells, found LMP2A expression enhanced not only BCR signals but also plasma-cell differentiation, in vitro and in vivo. Conditional LMP2A expression in GC B cells resulted in preferential selection of low-affinity antibody–producing B-cells despite apparently normal GC formation. GC B cell-specific LMP2A expression led to systemic lupus erythematosus-like autoimmune phenotypes in an age-dependent manner. Epigenetic profiling of LMP2A B cells found increased H3K27ac and H3K4me1 signals at the Zbtb20 locus. We conclude that LMP2A reduces the stringency of GC B cell selection and may contribute to persistent EBV infection and pathogenesis by providing GC B cells with pro-survival signals. Significance Statement: Epstein-Barr virus (EBV) is a human herpesvirus that establishes persistent infection of the B-cell compartment. EBV is associated with autoimmune diseases, including systemic lupus erythematosus (SLE). However, the molecular mechanisms by which EBV contributes to autoimmunity remain unclear. We used transgenic mouse models to study the role of EBV-encoded Latent membrane protein 2A (LMP2A), which mimics B-cell receptor signaling.　Interestingly, LMP2A not only enhanced B-cell survival, but also upregulated the transcription factor Zbtb20 and promoted plasma cell differentiation. When expressed late in B-cell development, LMP2A also caused prominent features of SLE, including autoantibody production with kidney immune complex deposition. Our findings suggest that LMP2A has important roles in B cell activation, differentiation and the development of EBV-associated autoimmune diseases.

Dataset Information

LMP2A mediated gene expression changes in transfected CD10+ GCB cells

Publications

Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle.

Similar Datasets

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