Meidan, E., Li, H., Pan, W., Kono, M., Yu, S., Kyttaris, V. C., Ioannidis, C., Rodriguez, R., Crispin, J. C., Apostolidis, S. A., Lee, P., Manis, J., Sharabi, A., Tsokos, M. G., & Tsokos, G. C. (2020). Serine/threonine phosphatase PP2A is essential for optimal B cell function. JCI Insight, 5.
Abstract
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 Cd19CrePpp2r1afl/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.
Last updated on 02/17/2024