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Open AccessResearch article

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

Jernej Murn1,2,3 email, Irena Mlinaric-Rascan2 email, Pierre Vaigot1 email, Olivier Alibert1 email, Vincent Frouin1 email and Xavier Gidrol1,4 email

1CEA, DSV, IRCM, Laboratoire d'Exploration Fonctionnelle des Génomes, Evry 91057, France

2Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia

3Current address : Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

4Current address : CEA, DSV, IRTSV, Laboratoire Biopuces, 17 rue des Martyrs, 38054 Grenoble Cedex 09, France

author email corresponding author email

BMC Genomics 2009, 10:323doi:10.1186/1471-2164-10-323

Published: 17 July 2009

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.


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