A Myc-regulated transcriptional network controls B-cell fate in response to BCR triggering

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.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/19607732
DOI: 10.1186/1471-2164-10-323

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: http://repository.cshl.edu/id/eprint/27422

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