Human pre‐B cell receptor signal transduction: evidence for distinct roles of PI3kinase and MAP‐kinase signalling pathways

Immunity, Inflammation and Disease

Kolandaswamy Anbazhagan¹  Amrathlal Rabbind Singh¹  Piec Isabelle¹  Ibata Stella¹  Alleaume-De Martel Céline¹  Eliane Bissac¹  Brassart Bertrand¹  Nyga Rémy¹  Taylor Naomi²  Fuentes Vincent¹  Jacques Rochette¹ 

[1] Inserm/UMR925, Université Picardie Jules Verne, Laboratoire d'Immunologie, UFR de Médecine, Amiens, France;CNRS/UMR 5535, Institut de Génétique Moléculaire de Montpellier, Montpellier, Cedex 5, France

关键词: MAPK;    PI3K;    pre‐B cells;    pre‐BCR;    receptor signalling;   

DOI  :  10.1002/iid3.4

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2013 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

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