Fig. 1

Upon antigen binding to the BCR, Src-family kinases such as LYN tyrosine kinase (LYN) and spleen tyrosine kinase (SYK) phosphorylate immunoreceptor tyrosine-based activation motif (ITAM) of Igα and Igβ, thereby recruiting spleen tyrosine kinase (SYK). SYK then phosphorylates and activates BTK. Subsequently, BTK phosphorylates phospholipase-Cg2 (PLCG2), and further initiates a series of downstream signaling pathways including nuclear factor kappa B (NF-kB), mitogen-activated protein kinase (MAPK), CaM and other pathways that promote cell proliferation and survival. In addition, BTK can also transmit various surface molecular signals such as Toll-like receptors (TLRs) that B cells communicate with the microenvironment; Tonic BCR: LYN also phosphorylates tyrosine residues in the cytoplasmic tail of the BCR co-receptor CD19, which countributes to the activation of phosphoinositol-3 kinase (PI3K) /AKT/mTOR signaling in antigen-independent manner