Fig. 3

Heterogeneous responses of normal and malignant B cells upon CpG ODNs stimulation. Activation of TLR9 results in the recruitment of MyD88 to initiate the activation of NF-κB, JNK, and p38 MAPK signaling pathways. Arrows represent activation. Bars represent inhibition. Activation of the NF-κB signaling pathway exerts both antiapoptotic and proapoptotic effects. In normal B cells (black lines), activation of NF-κB upregulates the expression of BCL-XL, which blocks cytochrome c release and protects B cells from apoptosis. However, upon treatment of the mouse B-cell lymphoma cell line CH27 with CpG ODNs, overexpression of c-Myc results in transient activation of NF-κB and subsequent inhibition of NF-κB activation (red bar). And then, c-Myc promotes tumor necrosis factor-induced apoptosis by decreasing BCL-XL expression and increasing FAS expression. In MM cells (purple lines), NF-κB is involved in the activation of Ras-dependent MAPK cascades and the JAK/STAT3 signaling pathway, which is associated with the proliferation of processed IL-6. In B-CLL cells (blue lines), activation of the NF-κB signaling pathway induces autocrine IL-10 secretion, which further induces phosphorylation and activation of the signal transducer and activator of transcription 1, resulting in the cleavage and activation of caspases as well as the subsequent apoptosis of B-CLL cells (MyD88 myeloid differentiation antigen 88, IFN interferon, CLL chronic lymphocytic leukemia, MM multiple myeloma, MAPK mitogen-activated protein kinases, PI3K phosphatidylinositol 3-kinase, DR5 death receptor 5, TRAIL TNF-related apoptosis-inducing ligand, STAT1 signal transducer and activator of transcription 1)