BCR-signaling pathway. The initial steps in the response to the activation of the BCR are the phosphorylation of the CD79 ITAM motifs by the kinase LYN, followed by the docking of SYK and the subsequent activation of different components of the signalosome, a molecular complex organized at the cell membrane that will expand the downstream signals.^31,34-39  This complex includes, among others, B-cell linker (BLNK), BTK, and PLCG2, together with PI3Kδ, recruited also by the adjacent activated CD19. The phosphorylation of the signalosome components propagates downstream messengers with the release of Ca²⁺ and diacylglycerol (DAG) and activation of protein kinase C (PKC), AKT, mitogen-activated protein kinase (MAPK) pathway with RAS/MEK/ERK, and the Rho-family GTPase among others. These signals lead to the activation of different transcriptions factors such as NF-κB, nuclear factor of activated T cells (NFAT), MYC, which result in the activation of cell survival and proliferation mechanisms, release of chemokines, and increase motility of the cells. The high expression of different elements such as IgM, ZAP70, and CD38 enhances the BCR response whereas other factors such as the phosphatase SHIP1, activated by LYN, act as a negative autoregulatory loop of the BCR stimulation. Other negative regulators are CD5, CD72, and CD22. Ag, antigen; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PTEN, phosphatase and tensin homolog.