Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M-induced B cell apoptosis.
Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-gamma 2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2 through Syk is required for sIgM-induced apoptosis.
Takata
M
M
Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, New York 10965, USA.
Homma
Y
Y
Kurosaki
T
T
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D001692:Biological Transport; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004249:DNA Damage; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006868:Hydrolysis; D007075:Immunoglobulin M / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000032:analysis; D015398:Signal Transduction; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
D004792:Enzyme Precursors; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D011976:Receptors, Muscarinic; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium