Research article
A Myc-regulated transcriptional network controls B-cell fate in response to BCR triggering
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* Corresponding author: Xavier Gidrol xavier.gidrol@cea.fr
1 CEA, DSV, IRCM, Laboratoire d'Exploration Fonctionnelle des Génomes, Evry 91057, France
2 Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
3 Current address : Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
4 Current address : CEA, DSV, IRTSV, Laboratoire Biopuces, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France
BMC Genomics 2009, 10:323 doi:10.1186/1471-2164-10-323
Published: 17 July 2009Abstract
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.