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

Charlotte Cresson (1) , Sophie Péron (2) , Laura Jamrog (1) , Nelly Rouquié (1) , Nais Prade (1) , Marine Dubois (1) , Sylvie Hébrard (1) , Stéphanie Lagarde (1) , Bastien Gerby (3) , Stéphane J.C. Mancini (4) , Michel Cogné (2) , Eric Delabesse (1) , Laurent Delpy (2) , Cyril Broccardo (1)

1 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
2 CRIBL - Contrôle de la Réponse Immune B et des Lymphoproliférations
3 CRCT - Centre de Recherches en Cancérologie de Toulouse
4 IPC - Institut Paoli-Calmettes

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.

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

Domaines: Cancer

Charlotte Cresson, Sophie Péron, Laura Jamrog, Nelly Rouquié, Nais Prade, et al.. PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation. Oncotarget, 2018, 9 (67), pp.32841-32854. ⟨10.18632/oncotarget.26003⟩. ⟨hal-02566158⟩