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

// Charlotte Cresson 1, * , Sophie Peron 2, * , Laura Jamrog 1, * , Nelly Rouquie 1 , Nais Prade 3 , Marine Dubois 1 , Sylvie Hebrard 1 , Stephanie Lagarde 3 , Bastien Gerby 1 , Stephane J.C. Mancini 4 , Michel Cogne 5 , Eric Delabesse 3 , Laurent Delpy 2 and Cyril Broccardo 1 1 Inserm, UMR1037 CRCT, F-31000, Universite Toulouse III-Paul Sabatier, UMR1037 CRCT, Oncopole, F-31000 Toulouse, France 2 Universite de Limoges-CNRS UMR 7276, F-87025 Limoges, France 3 Inserm, UMR1037 CRCT, F-31000, Universite Toulouse III-Paul Sabatier, UMR1037 CRCT, Toulouse Hospital University, Oncopole, CS 53717, F-31000 Toulouse, France 4 Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, F-13009 Marseille, France 5 Universite 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.