TY - JOUR
T1 - Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor-induced apoptosis
AU - Xing, Yan
AU - Igarashi, Hideya
AU - Wang, Xiaodan
AU - Sakaguchi, Nobuo
PY - 2005/9/5
Y1 - 2005/9/5
N2 - 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-κB, 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 NH2-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. JEM
AB - 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-κB, 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 NH2-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. JEM
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U2 - 10.1084/jem.20050637
DO - 10.1084/jem.20050637
M3 - Article
C2 - 16129705
AN - SCOPUS:24344443288
SN - 0022-1007
VL - 202
SP - 707
EP - 719
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -