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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

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Abstract

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 μg/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.

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Authors and Affiliations

  1. Department of Pediatrics, Yamada Red Cross Hospital, 810 Takabuku, Misono-mura, 5160805, Watarai-gun, Mie, Japan

    Masamune Higashigawa

  2. Department of Pediatrics, Mie University School of Medicine, Mie, Japan

    Masamune Higashigawa & Yoshihiro Komada

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  1. Masamune Higashigawa
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  2. Yoshihiro Komada
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Correspondence to Masamune Higashigawa.

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Higashigawa, M., Komada, Y. 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. Int J Hematol 76, 44–49 (2002). https://doi.org/10.1007/BF02982717

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  • DOI: https://doi.org/10.1007/BF02982717

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