Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor-induced apoptosis.
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.
Xing
Yan
Y
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Igarashi
Hideya
H
Wang
Xiaodan
X
Sakaguchi
Nobuo
N
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D017931:DNA Primers; D005434:Flow Cytometry; D020868:Gene Silencing; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051336:Mitochondrial Membranes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D017931:DNA Primers; C481510:GANP protein, mouse; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D048031:JNK Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases