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

摘要: Pre-BCR acts as a critical checkpoint in B cell development. However, its signalling cascade still remains indistinctly characterised human. We investigated pre-BCR pathway to examine regulation normal primary pre-B lymphocytes and lines. In lines, early events occurring after stimulation include phosphorylation of Lyn, Blk Syk together with ZAP70, Btk, Vav, PLC-γ2 various adaptor proteins, such BLNK, LAB, LAT SLP-76. Further downstream, these molecules induced activation the PI3K/AKT MAP-kinase resulting an augmentation canonical NF-κB pathways cFos/AP1 activation. PI3K MAPK exerted opposing effects on pre-BCR-induced c-Fos/AP1 pathways. Immediate nuclear export FoxO3A delayed import IRF4 were additional observed crosslinking cells. Pre-BCR-induced down-regulation Rag1, Rag2, E2A Pax5 transcripts occurred PI3K-dependent manner. Finally we bring evidence that or co CD19 enhances cycle signal.