IFN- α Sensitizes Daudi B Lymphoma Cells to Anti-IgMInduced Loss of Mitochondrial Membrane Potential Through Activation of c-Jun NH 2 -Terminal Kinase

Interferon-α (IFN-α) regulates multiple biologic functions, including antiviral activity, immune regulation, cell differentiation, and cell survival or death, in a variety of cell types. We and others have recently demonstrated that IFN-α induces cell death through activation of c-Jun NH₂-terminal kinase (JNK) in human Daudi B lymphoma and U266 myeloma cells. Moreover, the IFN-α-induced signaling pathway has been shown to cross talk with the antigen receptor-mediated signaling cascade. In the present study, we examined whether IFN-α affects cell death after engagement of membrane immunoglobulin (mIg) using anti-IgM. Daudi cells pretreated with low concentrations of IFN-α (25 or 250 U/mL) for 24 h were stimulated with anti-IgM (1–10µg/mL) for 24 h. The cells were assayed for JNK activation, mitochondrial membrane potential (ΔΨm) by Western blotting, and DiOC₆ staining, respectively. The IFN-α-primed Daudi cells showed an increased sensitivity to subsequent stimulation with anti-IgM, as assessed by JNK activation and ΔΨm. Moreover, Daudi cells overexpressing the constitutively active or dominant-negative form of JNK were substantially susceptible or resistant to anti-IgM-induced ΔΨm, respectively, compared with cells overexpressing the control vector alone. Taken together, these results indicate that IFN-α renders Daudi B lymphoma cells susceptible to anti-IgM-induced apoptosis, probably through upregulation of JNK activation.