IFN-γ Down-Regulates MHC Expression and Antigen Processing in a Human B Cell Line

Abstract

Abstract IFN-γ 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-γ 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-γ 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-γ 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.