Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells

J Immunol. 2012 Oct 15;189(8):3800-4. doi: 10.4049/jimmunol.1103080. Epub 2012 Sep 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • B-Lymphocyte Subsets / enzymology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Cell Line, Transformed
  • HLA-DR Antigens / metabolism*
  • Humans
  • Intracellular Fluid / enzymology
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • NADPH Oxidases / physiology*
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Reactive Oxygen Species / metabolism
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • HLA-DR Antigens
  • Phosphoproteins
  • Reactive Oxygen Species
  • neutrophil cytosol factor 40K
  • NADPH Oxidases