title: Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells.
abstract: Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive oxygen species (ROS) production. Defects in oxidase function result in chronic granulomatous disease with hallmark recurrent microbial infections and inflammation. The oxidase's role in the adaptive immune response is not well understood. Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T cells was impaired in human B cells with reduced oxidase p40(phox) subunit expression. Naturally arising mutations, which compromise p40(phox) function in a chronic granulomatous disease patient, also perturbed class II Ag presentation and intracellular ROS production. Reconstitution of patient B cells with a wild-type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and intracellular ROS generation. Remarkably, class II presentation of epitopes from membrane Ag was robust in p40(phox)-deficient B cells. These studies reveal a role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell recognition of self Ag.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Crotzer
authors.forename: Juan D
authors.initials: JD
authors.lastname: Matute
authors.forename: Andrés A
authors.initials: AA
authors.lastname: Arias
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Quilliam
authors.forename: Mary C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
mesh_terms: D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D019255:NADPH Oxidases / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C085072:neutrophil cytosol factor 40K; D019255:NADPH Oxidases