Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor-induced apoptosis

J Exp Med. 2005 Sep 5;202(5):707-19. doi: 10.1084/jem.20050637. Epub 2005 Aug 29.


B cell receptor (BCR) cross-linking induces B cell proliferation and sustains survival through the phosphorylation-dependent signals. We report that a loss of the protein phosphatase component G5PR increased the activation-induced cell death (AICD) and thus impaired B cell survival. G5PR associates with GANP, whose expression is up-regulated in mature B cells of the peripheral lymphoid organs. To study G5PR function, the G5pr gene was conditionally targeted with the CD19-Cre combination (G5pr(-/-) mice). The G5pr(-/-) mice had a decreased number of splenic B cells (60% of the controls). G5pr(-/-) B cells showed a normal proliferative response to lipopolysaccharide or anti-CD40 antibody stimulation but not to BCR cross-linking with or without IL-4 in vitro. G5pr(-/-) B cells did not show abnormalities in the BCR-mediated activation of Erks and NF-kappaB, cyclin D2 induction, or Akt activation. However, G5pr(-/-) B cells were sensitive to AICD caused by BCR cross-linking. This was associated with an increased depolarization of the mitochondrial membrane and the enhanced activation of c-Jun NH(2)-terminal protein kinase and Bim. These results suggest that G5PR is required for the BCR-mediated proliferation associated with the prevention of AICD in mature B cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism
  • B-Lymphocytes / physiology*
  • Bcl-2-Like Protein 11
  • Blotting, Western
  • DNA Primers
  • Flow Cytometry
  • Gene Silencing
  • In Situ Nick-End Labeling
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondrial Membranes / metabolism
  • Nuclear Proteins / metabolism
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphoproteins / metabolism
  • Protein Subunits / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Antigen, B-Cell / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • DNA Primers
  • GANP protein, mouse
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Receptors, Antigen, B-Cell
  • JNK Mitogen-Activated Protein Kinases
  • Phosphoprotein Phosphatases