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NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.

ABSTRACT: Defective reactive oxygen species (ROS) production by genetically determined variants of the NADPH oxidase 2 (NOX2) complex component, NCF4, leads to enhanced production of autoantibodies to collagen type II (COL2) and severe collagen-induced arthritis (CIA) in mice. To further understand this process, we used mice harboring a mutation in the lipid endosomal membrane binding site (R58A) of NCF4 subunit. This mutation did not affect the extracellular ROS responses but showed instead decreased intracellular responses following B cell stimulation. Immunization with COL2 led to severe arthritis with increased antibody levels in Ncf4^58A mutated animals without significant effects on antigen presentation, autoreactive T cell activation and germinal center formation. Instead, plasma cell formation was enhanced and had altered CXCR3/CXCR4 expression. This B cell intrinsic effect was further confirmed with chimeric B cell transfer experiments and in vitro LPS or CD40L with anti-IgM stimulation. We conclude that NCF4 regulates the terminal differentiation of B cells to plasma cells through intracellular ROS.

SUBMITTER: He C

PROVIDER: S-EPMC9482113 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.

He Chang C Luo Huqiao H Coelho Ana A Liu Meng M Li Qijing Q Xu Jing J Krämer Alexander A Malin Stephen S Yuan Zuyi Z Holmdahl Rikard R

Redox biology 20220827

Defective reactive oxygen species (ROS) production by genetically determined variants of the NADPH oxidase 2 (NOX2) complex component, NCF4, leads to enhanced production of autoantibodies to collagen type II (COL2) and severe collagen-induced arthritis (CIA) in mice. To further understand this process, we used mice harboring a mutation in the lipid endosomal membrane binding site (R58A) of NCF4 subunit. This mutation did not affect the extracellular ROS responses but showed instead decreased int ...[more]

PMID: 36095971

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NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.

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NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.

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