Murn, J., Mlinaric-Rascan, I., Vaigot, P., Alibert, O., Frouin, V., Gidrol, X.
(July 2009)
A Myc-regulated transcriptional network controls B-cell fate in response to BCR triggering.
BMC Genomics, 10.
p. 323.
Abstract
BACKGROUND: The B cell antigen receptor (BCR) is a signaling complex that mediates the differentiation of stage-specific cell fate decisions in B lymphocytes. While several studies have shown differences in signal transduction components as being key to contrasting phenotypic outcomes, little is known about the differential BCR-triggered gene transcription downstream of the signaling cascades. RESULTS: Here we define the transcriptional changes that underlie BCR-induced apoptosis and proliferation of immature and mature B cells, respectively. Comparative genome-wide expression profiling identified 24 genes that discriminated between the early responses of the two cell types to BCR stimulation. Using mice with a conditional Myc-deletion, we validated the microarray data by demonstrating that Myc is critical to promoting BCR-triggered B-cell proliferation. We further investigated the Myc-dependent molecular mechanisms and found that Myc promotes a BCR-dependent clonal expansion of mature B cells by inducing proliferation and inhibiting differentiation. CONCLUSION: This work provides the first comprehensive analysis of the early transcriptional events that lead to either deletion or clonal expansion of B cells upon antigen recognition, and demonstrates that Myc functions as the hub of a transcriptional network that control B-cell fate in the periphery.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Animals
Apoptosis
B-Lymphocytes/*cytology/immunology
Cell Differentiation
Cell Proliferation
Cells, Cultured
Comparative Genomic Hybridization
Gene Expression Profiling
Gene Expression Regulation
*Gene Regulatory Networks
Genome-Wide Association Study
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc/genetics/*metabolism
Receptors, Antigen, B-Cell/immunology/*metabolism
*Signal Transduction |
| Subjects: |
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
organs, tissues, organelles, cell types and functions |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Trotman lab |
| Depositing User: |
Matt Covey
|
| Date: |
17 July 2009 |
| Date Deposited: |
20 Feb 2013 17:55 |
| Last Modified: |
20 Feb 2013 17:55 |
| PMCID: |
PMC2722676 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/27422 |
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