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¹ Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan
² Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan

CORRESPONDENCE Nobuo Sakaguchi: nobusaka{at}kaiju.medic.kumamoto-u.ac.jp

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-B, 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.

Abbreviations used: Ab, antibody; Ag, antigen; AICD, activation-induced cell death; BCR, B cell receptor; m, mitochondrial membrane potential; GC, germinal center; JNK, c-Jun NH₂-terminal protein kinase; MAPK, mitogen- activated protein kinase; PP, protein phosphatase; SRBC, sheep RBC; TUNEL, Tdt-mediated dUTP-biotin nick-end labeling.

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