NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation
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 proce...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172200194X |
| _version_ | 1828237835909464064 |
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| author | Chang He Huqiao Luo Ana Coelho Meng Liu Qijing Li Jing Xu Alexander Krämer Stephen Malin Zuyi Yuan Rikard Holmdahl |
| author_facet | Chang He Huqiao Luo Ana Coelho Meng Liu Qijing Li Jing Xu Alexander Krämer Stephen Malin Zuyi Yuan Rikard Holmdahl |
| author_sort | Chang He |
| collection | DOAJ |
| description | 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 Ncf458A 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. |
| first_indexed | 2024-04-12T20:54:46Z |
| format | Article |
| id | doaj.art-7a75ebf3855c41f6a4e5909bf8aeeb0e |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T20:54:46Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-7a75ebf3855c41f6a4e5909bf8aeeb0e2022-12-22T03:17:02ZengElsevierRedox Biology2213-23172022-10-0156102422NCF4 dependent intracellular reactive oxygen species regulate plasma cell formationChang He0Huqiao Luo1Ana Coelho2Meng Liu3Qijing Li4Jing Xu5Alexander Krämer6Stephen Malin7Zuyi Yuan8Rikard Holmdahl9Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDivision of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenDivision of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenXi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; National Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaXi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China; Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Hematology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR ChinaDivision of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenDepartment of Medicine Solna (MedS) Center for Molecular Medicine, Karolinska Institute, Stockholm, SwedenDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDivision of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; National Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Corresponding author. Division of Medical Inflammation Research, Dept. of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.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 Ncf458A 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.http://www.sciencedirect.com/science/article/pii/S221323172200194XNeutrophil cytosolic factor 4Redox regulationB cellPlasma cellAutoimmunityOxidative eustress |
| spellingShingle | Chang He Huqiao Luo Ana Coelho Meng Liu Qijing Li Jing Xu Alexander Krämer Stephen Malin Zuyi Yuan Rikard Holmdahl NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation Redox Biology Neutrophil cytosolic factor 4 Redox regulation B cell Plasma cell Autoimmunity Oxidative eustress |
| title | NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| title_full | NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| title_fullStr | NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| title_full_unstemmed | NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| title_short | NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| title_sort | ncf4 dependent intracellular reactive oxygen species regulate plasma cell formation |
| topic | Neutrophil cytosolic factor 4 Redox regulation B cell Plasma cell Autoimmunity Oxidative eustress |
| url | http://www.sciencedirect.com/science/article/pii/S221323172200194X |
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