| First Author | He C | Year | 2022 |
| Journal | Redox Biol | Volume | 56 |
| Pages | 102422 | PubMed ID | 36095971 |
| Mgi Jnum | J:336687 | Mgi Id | MGI:7341026 |
| Doi | 10.1016/j.redox.2022.102422 | Citation | He C, et al. (2022) NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation. Redox Biol 56:102422 |
| abstractText | 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. |
