Abstract
IFNs are a family of cytokines that are involved in the regulation of immune and inflammatory responses. Clinical use of IFN-alpha/beta encompasses treatment for a variety of diseases; however, prolonged exposure to IFN-alpha/beta 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-alpha or IFN-beta 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-alpha and IFN-beta, but not IFN-gamma, significantly increase the levels of the survival protein Bcl-2, and to a lesser extent, Bcl-xL expression. Thus, IFN-alpha/beta-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Antibodies, Anti-Idiotypic / physiology
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Apoptosis / drug effects
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Apoptosis / immunology*
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Burkitt Lymphoma
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CD40 Antigens / metabolism
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CD40 Antigens / physiology
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Enzyme Inhibitors / pharmacology
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Genistein / pharmacology
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Humans
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Immunosuppressive Agents / pharmacology*
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Interferon-alpha / pharmacology*
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Interferon-beta / pharmacology*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Antigen, B-Cell / physiology*
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Sirolimus / pharmacology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Tumor Cells, Cultured
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Wortmannin
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bcl-X Protein
Substances
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Androstadienes
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Antibodies, Anti-Idiotypic
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BCL2L1 protein, human
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CD40 Antigens
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Enzyme Inhibitors
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Immunosuppressive Agents
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Interferon-alpha
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, B-Cell
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anti-IgM
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bcl-X Protein
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Interferon-beta
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Genistein
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Sirolimus
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Wortmannin