Serine/threonine phosphatase PP2A is essential for optimal B cell function

JCI Insight. 2020 Mar 12;5(5):e130655. doi: 10.1172/jci.insight.130655.


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.

Keywords: Autoimmunity; B cells; Immunology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoimmunity
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Germinal Center / immunology
  • Humans
  • Lupus Erythematosus, Systemic / enzymology
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Protein Phosphatase 2 / metabolism*
  • T-Lymphocytes / immunology


  • Autoantibodies
  • Protein Phosphatase 2