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

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Phagocyte NADPH oxidase generates reactive oxygen species (ROS) essential for pathogen clearance.
• Defects in NADPH oxidase cause chronic granulomatous disease (CGD), characterized by infections and inflammation.
• The role of NADPH oxidase in adaptive immunity, particularly antigen presentation, remains incompletely understood.

Purpose of the Study:

• To investigate the function of the p40(phox) subunit of NADPH oxidase in antigen presentation by B cells.
• To determine how mutations affecting p40(phox) function influence adaptive immune responses.
• To elucidate the role of NADPH oxidase in T cell recognition of self and foreign antigens.

Main Methods:

• Analysis of antigen presentation in human B cells with reduced or mutated p40(phox) expression.
• Assessment of intracellular ROS production in B cells.
• Restoration of p40(phox) function in patient-derived B cells to evaluate its impact on antigen presentation.

Main Results:

• Reduced p40(phox) expression impaired class II antigen presentation of cytoplasmic and exogenous antigens to CD4(+) T cells.
• Naturally occurring mutations compromising p40(phox) function similarly affected antigen presentation and ROS production.
• Restoration of wild-type p40(phox) normalized antigen presentation and ROS generation, while a mutant version did not.
• Class II presentation of membrane-associated antigens remained robust in p40(phox)-deficient B cells.

Conclusions:

• NADPH oxidase, specifically the p40(phox) subunit, plays a critical role in regulating antigen presentation by B cells.
• p40(phox) influences epitope selection, impacting T cell recognition of antigens.
• These findings highlight a novel function for NADPH oxidase in shaping adaptive immune responses and self-antigen recognition.