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

Esra Meidan1,2, Hao Li1, Wenliang Pan1

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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.

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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.