Overexpression of the death-promoting gene bax-alpha sensitizes human BL-41 Burkitt lymphoma cells for surface IgM-mediated apoptosis.
Major regulators of programmed cell death, or apoptosis, are the members of the bcl-2 gene family. Recently, we reported that surface(s) IgM triggering of the human B lymphoma cell line BL-41 led to strong induction of bax-alpha, a death-promoting member of the bcl-2 family, and subsequently to induction of apoptosis, suggesting a potential regulatory role of bax-alpha in sIgM-mediated cell death. In contrast, apoptosis-resistant subclones of this cell line showed only weak bax-alpha expression, which was not inducible by sIgM cross-linking. In this study, we were able to demonstrate the functional significance of this observation. We stably transfected bax-alpha into a BL-41 subline resistant against sIgM-mediated apoptosis. Several bax-alpha overexpressing clones could be selected, which all showed enhanced sensitivity for sIgM-mediated apoptosis. In contrast, no sensitive clone could be identified in a large number of mock controls. This clearly indicates that induction of bax-alpha is a critical regulatory step, which sensitizes B cells for sIgM-mediated apoptosis.
Weinmann
P
P
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Bommert
K
K
Mapara
M Y
MY
Dörken
B
B
Bargou
R C
RC
D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000473:pathology*; D018014:Gene Transfer Techniques; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D007075:Immunoglobulin M; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D051028:bcl-2-Associated X Protein