Abstract
IFN-gamma is a crucial mediator in the induction of cell-mediated Th1-type responses but is predominantly a negative regulator of B cell differentiation and proliferation. This cytokine is therefore a key factor in determining Th1 vs Th2 differentiation. This study investigates the action of IFN-gamma in modulation of HLA-DR expression and Ag presentation by EBV-transformed human B cell lines. In contrast to its action on the monocyte/macrophage, IFN-gamma down-regulates surface MHC expression on these B cells, and this regulation is posttranscriptional. In parallel with MHC down-regulation, there is a reduced capability to process and present exogenous protein and peptide Ag to T cell hybridomas. IFN-gamma does not change the rates of fluid phase endocytosis or exocytosis in this model system but correlates with an up-regulation of the lysosomal enzymes cathepsins B and D.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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Apoptosis / immunology
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B-Lymphocytes / enzymology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism*
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Cathepsins / antagonists & inhibitors
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Cathepsins / biosynthesis
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Cathepsins / metabolism
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Cell Line, Transformed
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Down-Regulation / immunology*
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Endocytosis / immunology
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HLA-D Antigens / metabolism
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Histocompatibility Antigens Class II / biosynthesis*
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Histocompatibility Antigens Class II / genetics
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Humans
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Hybridomas / immunology
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Hybridomas / metabolism
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Interferon-gamma / pharmacology*
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Mice
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Muramidase / immunology
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Muramidase / metabolism
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Transfection / immunology
Substances
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H2-M antigens
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HLA-D Antigens
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HLA-DM antigens
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Histocompatibility Antigens Class II
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Interferon-gamma
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Muramidase
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Cathepsins