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| Status |
Public on Jan 01, 2011 |
| Title |
Comparative gene expression analysis upon stimulation of the human BCR or an inducible LMP2A in EBV immortalized lymphoblastoid cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Survival of all B cells depends on signals from the B-cell receptor (BCR). In BCRnegative B cells the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) replaces this survival signal and might play a role in the development of EBV-positive Hodgkin lymphomas and posttransplantation lymphoproliferative disease. In these BCR-negative cells LMP2A provides a ‘tonic’ signal similar to BCR’s constitutive expression in the absence of antigen in order to maintain activating signaling pathways common to both receptor molecules. In most latently EBV-infected B cells LMP2A and BCR are co-expressed but it is largely unclear what LMP2A contributes with respect to B-cell activation, proliferation and viral latency in these BCR-positive cells. A common model suggests that LMP2A maintains herpesviral latency by blocking BCR-mediated signals but how LMP2A could serve both antithetical ends in BCRnegative and BCR-positive cells is elusive.
Our comparative analysis of BCR and LMP2A now indicates that LMP2A is a true BCR mimic that dominates BCR-operated signaling pathways in EBV-infected, BCR-positive cells to provide activation signals, support stable infections in vivo and allow exit from latency. These findings suggest that LMP2A co-opts the situation in anergic B cells, where continuous BCR signaling results in maintenance of the anergic state accompanied by unresponsiveness to acute BCR stimulation. The microarray experiment was used to compare effects of BCR and LMP2A on gene expression regulation. EBV's LMP2A and the human BCR activate similar cellular target genes; some genes are regulated solely by BCR or LMP2A, no gene is counter regulated
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| Overall design |
A 12 chip study using cDNA from three separate 2525 LMP2A knockout LCL cultures and three separate 3696.10 LMP2A:mCD69 LCL cultures; each culture tested before and after 90 min stimulation of the BCR and LMP2A:mCD69, respectively.
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| Contributor(s) |
Medele S, Mancao C, Matskova L, Bauer C, Hammerschmidt W |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 17, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Wolfgang Hammerschmidt |
| E-mail(s) |
[email protected]
|
| Organization name |
Helmholtz Zentrum München
|
| Department |
Gene Vectors
|
| Street address |
Marchioninistr. 25
|
| City |
Munich |
| ZIP/Postal code |
81377 |
| Country |
Germany |
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| Platforms (1) |
| GPL11219 |
NimbleGen Homo sapiens HG18 60mer expr (385k) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA133791 |
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