These authors contributed equally to this work.
Human pre-B cell receptor signal transduction: evidence for distinct roles of PI3kinase and MAP-kinase signalling pathways
Article first published online: 24 SEP 2013
© 2013 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Immunity, Inflammation and Disease
Volume 1, Issue 1, pages 26–36, October 2013
How to Cite
Anbazhagan, K., Rabbind Singh, A., Isabelle, P., Stella, I., Céline, A.-D. M., Bissac, E., Bertrand, B., Rémy, N., Naomi, T., Vincent, F., Rochette, J. and Lassoued, K. (2013), Human pre-B cell receptor signal transduction: evidence for distinct roles of PI3kinase and MAP-kinase signalling pathways. Immunity, Inflammation and Dis, 1: 26–36. doi: 10.1002/iid3.4
This work was supported by grants from INSERM, Conseil Régional de Picardie, Association pour la Recherche sur le Cancer, Fondation pour la Recherche Médicale, Fondation de France, Association Cent pour Sang la Vie, la Ligue contre le Cancer and CHU D'Amiens.
- Issue published online: 29 OCT 2013
- Article first published online: 24 SEP 2013
- Manuscript Accepted: 11 JUL 2013
- Manuscript Revised: 8 JUL 2013
- Manuscript Received: 5 APR 2013
- FeDER, Conseil Régional de Picardie and Centre Hospitalier Universitaire D'Amiens
- pre-B cells;
- receptor signalling
Pre-BCR acts as a critical checkpoint in B cell development. However, its signalling cascade still remains indistinctly characterised in human. We investigated pre-BCR signalling pathway to examine its regulation in normal primary pre-B lymphocytes and pre-B cell lines. In cell lines, early signalling events occurring after pre-BCR stimulation include phosphorylation of Lyn, Blk and Syk together with ZAP70, Btk, Vav, PLC-γ2 and various adaptor proteins, such as BLNK, LAB, LAT and SLP-76. Further downstream, these molecules induced activation of the PI3K/AKT and MAP-kinase resulting in an augmentation of canonical NF-κB pathways and cFos/AP1 activation. PI3K and MAPK exerted opposing effects on the pre-BCR-induced activation of the canonical NF-κB and c-Fos/AP1 pathways. Immediate nuclear export of FoxO3A and delayed import of IRF4 were additional events observed after pre-BCR crosslinking in primary cells. Pre-BCR-induced down-regulation of Rag1, Rag2, E2A and Pax5 transcripts occurred in a PI3K-dependent manner. Finally we bring evidence that pre-BCR stimulation or co stimulation with CD19 enhances cell cycle signal.