First Author | Meidan E | Year | 2020 |
Journal | JCI Insight | Volume | 5 |
Issue | 5 | PubMed ID | 32161189 |
Mgi Jnum | J:301820 | Mgi Id | MGI:6505373 |
Doi | 10.1172/jci.insight.130655 | Citation | Meidan E, et al. (2020) Serine/threonine phosphatase PP2A is essential for optimal B cell function. JCI Insight 5(5) |
abstractText | 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. |