Inhibition of B cell receptormediated apoptosis by IFN

IFNs are a family of cytokines that are involved in the regulation of immune and inflammatory responses. Clinical use of IFN-a/b encompasses treatment for a variety of diseases; however, prolonged exposure to IFN-a/b results in elevated levels of autoreactive Abs. In this study, we investigated the potential of IFNs to modulate apoptotic signals in B cells. We demonstrate that IFN-a or IFN-b inhibit Ag receptor-mediated apoptosis in a dose-dependent manner. Inhibition of phosphatidylinositol 3 * (PI3)-kinase did not abolish the effect of IFN, indicating that the antiapoptotic mechanism is PI3-kinase- and protein kinase B/Akt-independent. Instead, IFN-a and IFN-b, but not IFN-g, significantly increase the levels of the survival protein Bcl-2, and to a lesser extent, Bcl-xL expression. Thus, IFN-a/b-mediated inhibition of B cell Ag receptor-triggered apoptosis may offer a model for the process that leads to the escape of self-reactive B cells from negative selection and consequently results in autoantibody production. The Journal of Immunology, 1999, 162: 6317–6321. I nterferons stand out among the members of the cytokine su-perfamily through their unique pleiotropy of biological ef-fects, which encompass growth inhibition, antiviral defense, and immunomodulatory properties (1, 2). Consequently, IFNs find diverse clinical application in the treatment of tumors (particularly of hematologic and dermatologic malignancies), as well as in the therapy of viral infections (hepatitis C) or immunological disorders (multiple sclerosis, myasthenia gravis). Therapy with type I IFNs