International Immunology Advance Access originally published online on May 17, 2004
International Immunology 2004 16(7):971-982; doi:10.1093/intimm/dxh100
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International Immunology, Vol. 16, No. 7, pp. 971-982,
July 2004
© 2004 Japanese Society for Immunology
Impairment of B cell receptor-mediated Ca2+ influx, activation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells
1 Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo 183-8526, Japan 2 School of Health Sciences, Tokai University, Isehara, Kanagawa 259-1193, Japan 3 Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan 4 Present address: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
Correspondence to: H. Yakura; E-mail: yakura{at}tmin.ac.jp
Transmitting editor: T. Watanabe
CD72 is a 45 kDa B cell-specific type II transmembrane protein of the C-type lectin superfamily. It was originally defined as a receptor-like molecule that regulates B cell activation and differentiation; however, its precise function remains unclear since more recent functional analyses, including a gene targeting study, suggest that CD72 may serve as a negative or a positive regulator of B cell signaling. In the present study, we analyzed the cell-autonomous function of CD72 in B cell receptor (BCR) signaling using CD72-deficient cells generated from mature BAL-17 cells. We found that BCR-mediated phosphorylation of CD19, Btk, Vav and phospholipase C
2 and association of CD19 with phosphatidylinositol-3 kinase were impaired in CD72-deficient cells. Inositol trisphosphate synthesis was normally induced initially but ablated at 1 min of stimulation in CD72-deficient cells. In the event, Ca2+ release from intracellular stores remained intact, though influx of extracellular Ca2+ was severely impaired in CD72-deficient cells. Furthermore, BCR-evoked activation of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase and c-Jun NH2-terminal kinase, and growth inhibition in BAL-17 cells were blocked in the absence of CD72. Significantly, these effects were largely reversed by re-expression of CD72. Thus, CD72 appears to exert a positive effect on BCR signaling pathways leading to Ca2+ influx and MAPK activation, which in turn may determine the fate of BAL-17 cells.
Keywords: B cell antigen receptor, calcium entry, CD19, PI3 kinase
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