Serine/threonine phosphatase PP2A is essential for optimal B cell function
| Autor: | Hao Li, George C. Tsokos, Pui Lee, Amir Sharabi, Michihito Kono, Maria Tsokos, Esra Meidan, John P. Manis, Vasileios C. Kyttaris, José C. Crispín, Christina Ioannidis, Sokratis A. Apostolidis, Shuilian Yu, Wen Liang Pan, Noe Rodriguez Rodriguez |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
T-Lymphocytes T cell Purine nucleoside phosphorylase Autoimmunity Enzyme-Linked Immunosorbent Assay Mice Transgenic Nicotinamide adenine dinucleotide Lymphocyte Activation Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antigen FLOX medicine Animals Humans Lupus Erythematosus Systemic Protein Phosphatase 2 B cell Autoantibodies B-Lymphocytes Chemistry Germinal center General Medicine Protein phosphatase 2 Flow Cytometry Germinal Center Molecular biology 030104 developmental biology medicine.anatomical_structure Case-Control Studies 030220 oncology & carcinogenesis Research Article |
| Zdroj: | JCI Insight. 5 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.130655 |
| Popis: | Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro–activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19(Cre)Ppp2r1a(fl/fl) (flox/flox) mouse which lacks functional PP2A only in B cells. Flox/flox mice displayed reduced spontaneous germinal center formation and decreased responses to T cell-dependent and T-independent antigens, while their B cells responded poorly in vitro to stimulation with an anti-CD40 antibody or CpG in the presence of IL-4. Transcriptome and metabolome studies revealed altered nicotinamide adenine dinucleotide (NAD) and purine/pyrimidine metabolism and increased expression of purine nucleoside phosphorylase in PP2A-deficient B cells. Our results demonstrate that PP2A is required for optimal B cell function and may contribute to increased B cell activity in systemic autoimmunity. |
| Databáze: | OpenAIRE |
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