Role of Ca2+ in the intracellular signaling pathway of anti-IgM-induced apoptosis in the human B-cell line, MBC-1, established from Burkitt lymphoma.
The role of Ca2+ in the intracellular signal transduction process that causes antibody-induced apoptotic cell death in B-cells is not completely understood. We previously established a B-cell line (MBC-1) from a patient with Burkitt lymphoma at the leukemic stage that demonstrated the typical morphology and internucleosomal DNA fragmentation of apoptosis when treated with anti-immunoglobulin (Ig)M antibody. This antibody-induced cell death was partially inhibited by pretreatment with ethyleneglycol-bis-tetraacetic acid (EGTA) and actinomycin-D. FK506, an immunosupressive agent and calcineurin inhibitor, also partially rescued the anti-IgM antibody-induced death of MBC-1 cells. These results show that the calcium signaling pathway, which leads to a change in gene expression, plays an important role in anti-IgM-induced apoptosis in MBC-1 cells. Flow cytometric measurement of the cytosolic free Ca2+ concentration ([Ca2+]i) showed that nontoxic concentrations of 4-bromo-calcium ionophore A23187 (Ca2+ IP) increased [Ca2+]i more than did the anti-IgM antibody. A brief Ca2+ spike was observed on anti-IgM antibody treatment, but a gradual increase and decrease were observed when the cells were treated with Ca2+ IP at a nontoxic concentration of 1 microg/mL. These findings suggest that interpretations differ for the 2 patterns of calcium signaling and that the brief spiked elevation of Ca2+ produces distinct biological and cellular responses compared to the gradual increase and decrease of [Ca2+]i. Our results support the hypothesis that Ca2+ plays a significant role as a multifunctional second messenger providing specific information to the nucleus in anti-IgM antibody-induced apoptosis in MBC-1 cells.
Department of Pediatrics, Yamada Red Cross Hospital, Mie, Japan. higashigawa@hotmail.com
Masamune
M
Higashigawa
Yoshihiro
Y
Komada
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003609:Dactinomycin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D007476:Ionophores; C044203:anti-IgM; D003609:Dactinomycin; D004533:Egtazic Acid; D002118:Calcium; D016559:Tacrolimus