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


CONCLUSIONS
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.
Murn
Jernej
J
CEA, DSV, IRCM, Laboratoire d'Exploration Fonctionnelle des Génomes, Evry 91057, France. murn@cshl.edu
Mlinaric-Rascan
Irena
I
Vaigot
Pierre
P
Alibert
Olivier
O
Frouin
Vincent
V
Gidrol
Xavier
X
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D055028:Comparative Genomic Hybridization; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell