IFN-gamma down-regulates MHC expression and antigen processing in a human B cell line

IFN-gamma is a crucial mediator in the induction of cell-mediated Th1-type responses but is predominantly a negative regulator of B cell differentiati on and proliferation. This cytokine is therefore a hey factor in determinin g Th1 vs Th2 differentiation, This study investigates the action of IFN-gam ma in modulation of HLA-DR expression and Ag presentation by EBV-transforme d 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, t here is a reduced capability to process and present exogenous protein and p eptide Ag to T cell hybridomas. IFN-gamma does not change the rates of flui d phase endocytosis or exocytosis in this model system but correlates with an up-regulation of the lysosomal enzymes cathepsins B and D.