Oncotarget

Research Papers:

PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation

Charlotte Cresson, Sophie Péron, Laura Jamrog, Nelly Rouquié, Nais Prade, Marine Dubois, Sylvie Hébrard, Stéphanie Lagarde, Bastien Gerby, Stéphane J.C. Mancini, Michel Cogné, Eric Delabesse, Laurent Delpy and Cyril Broccardo _

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Oncotarget. 2018; 9:32841-32854. https://doi.org/10.18632/oncotarget.26003

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Abstract

Charlotte Cresson1,*, Sophie Péron2,*, Laura Jamrog1,*, Nelly Rouquié1, Nais Prade3, Marine Dubois1, Sylvie Hébrard1, Stéphanie Lagarde3, Bastien Gerby1, Stéphane J.C. Mancini4, Michel Cogné5, Eric Delabesse3, Laurent Delpy2 and Cyril Broccardo1

1Inserm, UMR1037 CRCT, F-31000, Université Toulouse III-Paul Sabatier, UMR1037 CRCT, Oncopole, F-31000 Toulouse, France

2Université de Limoges-CNRS UMR 7276, F-87025 Limoges, France

3Inserm, UMR1037 CRCT, F-31000, Université Toulouse III-Paul Sabatier, UMR1037 CRCT, Toulouse Hospital University, Oncopole, CS 53717, F-31000 Toulouse, France

4Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, F-13009 Marseille, France

5Université de Limoges-CNRS UMR 7276, Institut Universitaire de France, F-87025 Limoges, France

*These authors contributed equally to this work

Correspondence to:

Cyril Broccardo, email: cyril.broccardo@inserm.fr

Keywords: Pax5; transcription factor; B cell development; B cells; acute lymphoblastic leukemia

Received: August 11, 2016     Accepted: July 31, 2018     Published: August 28, 2018

ABSTRACT

Pax5 is the guardian of the B cell identity since it primes or enhances the expression of B cell specific genes and concomitantly represses the expression of B cell inappropriate genes. The tight regulation of Pax5 is therefore required for an efficient B cell differentiation. A defect in its dosage can translate into immunodeficiency or malignant disorders such as leukemia or lymphoma.

Pax5 is expressed from two different promoters encoding two isoforms that only differ in the sequence of their first alternative exon. Very little is known regarding the role of the two isoforms during B cell differentiation and the regulation of their expression. Our work aims to characterize the mechanisms of regulation of the expression balance of these two isoforms and their implication in the B cell differentiation process using murine ex vivo analyses. We show that these two isoforms are differentially regulated but have equivalent function during early B cell differentiation and may have functional differences after B cell activation. The tight control of their expression may thus reflect a way to finely tune Pax5 dosage during B cell differentiation process.


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