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.

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 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.

• Authors: Masamune Higashigawa, Yoshihiro Komada
• Journal: International journal of hematology (Int J Hematol) Vol. 76 Issue 1 Pg. 44-9 (Jul 2002) ISSN: 0925-5710 [Print] Japan
• PMID: 12138894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Ionophores
• anti-IgM
• Dactinomycin
• Egtazic Acid
• Calcium
• Tacrolimus

Topics

• Antibodies, Anti-Idiotypic (pharmacology)
• Apoptosis (drug effects, immunology)
• Calcium (physiology)
• Cell Death (drug effects, immunology)
• Dactinomycin (pharmacology)
• Egtazic Acid (pharmacology)
• Humans
• Ionophores (pharmacology)
• Signal Transduction
• Tacrolimus (pharmacology)
• Tumor Cells, Cultured