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BMC Genomics. 2009 Jul 17;10:323. doi: 10.1186/1471-2164-10-323.

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

Author information

1
CEA, DSV, IRCM, Laboratoire d'Exploration Fonctionnelle des Génomes, Evry 91057, France. murn@cshl.edu

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.

PMID:
19607732
PMCID:
PMC2722676
DOI:
10.1186/1471-2164-10-323
[Indexed for MEDLINE]
Free PMC Article

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