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Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
Serine/threonine phosphatase PP2A is essential for optimal B cell function
Esra Meidan1,2, Hao Li1, Wenliang Pan1
1Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Boston, Massachusetts, USA.
Protein phosphatase 2A (PP2A) is crucial for B cell function. This study shows PP2A deficiency impairs B cell responses and metabolism, suggesting its role in autoimmune diseases like lupus.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Protein phosphatase 2A (PP2A) regulates T cell function.
- Increased PP2A activity is observed in B cells from lupus-prone mice and patients with systemic lupus erythematosus (SLE).
Purpose of the Study:
- To investigate the role of PP2A in B cell function.
- To determine PP2A's contribution to B cell activity in autoimmunity.
Main Methods:
- Generated a B cell-specific PP2A knockout mouse model (Cd19CrePpp2r1afl/fl).
- Assessed B cell responses in vitro and in vivo.
- Performed transcriptome and metabolome analyses.
Main Results:
- PP2A-deficient B cells showed reduced germinal center formation and impaired responses to T cell-dependent and T-independent antigens.
- In vitro stimulation of PP2A-deficient B cells with anti-CD40/IL-4 or CpG/IL-4 yielded poor responses.
- Altered nicotinamide adenine dinucleotide (NAD) and purine/pyrimidine metabolism, with increased purine nucleoside phosphorylase expression, was observed in PP2A-deficient B cells.
Conclusions:
- PP2A is essential for optimal B cell function.
- PP2A may play a role in the heightened B cell activity observed in systemic autoimmune diseases.
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