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

VL Crotzer, JD Matute, AA Arias, H Zhao… - The Journal of …, 2012 - journals.aai.org
VL Crotzer, JD Matute, AA Arias, H Zhao, LA Quilliam, MC Dinauer, JS Blum
The Journal of Immunology, 2012journals.aai.org
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 …
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.
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