Human pre‐ B cell receptor signal transduction: evidence for distinct roles of PI 3 k inase and MAP ‐ k inase signalling pathways

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2013-10, Vol.1 (1), p.26-36
• Main Authors: Anbazhagan, Kolandaswamy, Rabbind Singh, Amrathlal, Isabelle, Piec, Stella, Ibata, Céline, Alleaume‐De Martel, Bissac, Eliane, Bertrand, Brassart, Rémy, Nyga, Naomi, Taylor, Vincent, Fuentes, Rochette, Jacques, Lassoued, Kaïss
• Format: Article
• Language: English
• Subjects: Cell cycle; Gene expression; Kinases; Phosphorylation; Real time; Signal transduction; Software; Statistical analysis; Transcription factors
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.4

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.