Anti-IgM antibody-induced cell death in a human B lymphoma cell line, B104, represents a novel programmed cell death.
We investigated the mechanisms of anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B lymphoma cell line, B104, the growth of which is irreversibly inhibited by anti-IgM antibody but not by anti-IgD antibody, and compared it with the cell death of T cells via TCR/CD3 complex and with the cell death of a murine anti-IgM antibody-sensitive B lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover, cyclosporin A rescued B104 cells from this lethal signal, via surface IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface IgM cross-linking represents a hitherto undefined mode of programmed cell death.
Ishigami
T
T
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Kim
K M
KM
Horiguchi
Y
Y
Higaki
Y
Y
Hata
D
D
Heike
T
T
Katamura
K
K
Mayumi
M
M
Mikawa
H
H
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D003609:Dactinomycin; D016572:Cyclosporine; D004247:DNA; D003513:Cycloheximide; D002118:Calcium