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Characterization of transforming growth factor-beta 1 induced apoptosis in normal human B cells and lymphoma B cell
N Chaouchi1, L Arvanitakis, M T Auffredou
1INSERM U131, Clamart, France.
Abstract:
Transforming growth factor beta 1 (TGF beta 1) has been shown to inhibit growth stimulation in normal human B cells as well as in Epstein Barr virus (EBV)-negative Burkitt's lymphoma (BL) cell lines. The mechanisms for this potent growth inhibition are not completely defined. Here we show that a number of EBV-negative lymphoma B cell lines (BL-41, Ramos and CAPA-2), when exposed in vitro to TGF beta 1, undergo apoptosis. Maximum apoptosis was observed at 48 h following TGF beta 1 treatment, with no apparent effect on the expression of c-myc and bcl-2 proteins. Similar induction of apoptosis was observed when these lymphoma cell lines were treated with aphidicolin, a DNA synthesis inhibitor. In contrast, various preparations (14 out of 17) of normal human tonsilar B cells showed no significant apoptosis, although both TGF beta 1 and aphidicolin inhibited anti-mu/IL-4 induced DNA synthesis in all preparations. Furthermore, another TGF beta 1 sensitive EBV-negative BL cell line, CA46, exhibited no apoptosis in response to TGF beta 1 and aphidicolin, corroborating the findings in normal human B cells. Taken together, these data support the hypothesis that exposure to TGF beta 1, which results in cell cycle arrest and DNA synthesis inhibition, may not be obligatory or sufficient for the induction of apoptosis. Rather, induction of apoptosis or lack of it may be intrinsically determined by an interplay between extracellular and intracellular regulators of cellular growth.
Insights
Transforming growth factor beta 1 (TGF beta 1) induces apoptosis in some Epstein Barr virus-negative lymphoma B cells. This cell death is not always linked to growth inhibition, suggesting intrinsic cellular factors regulate apoptosis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor beta 1 (TGF beta 1) is known to inhibit growth in normal human B cells and Epstein Barr virus (EBV)-negative Burkitt's lymphoma (BL) cell lines.
- The precise mechanisms underlying TGF beta 1's potent growth inhibition are not fully elucidated.
Purpose of the Study:
- To investigate the mechanisms of growth inhibition by TGF beta 1 in EBV-negative lymphoma B cells.
- To determine if TGF beta 1-induced growth inhibition leads to apoptosis in these cell lines.
Main Methods:
- Exposure of EBV-negative lymphoma B cell lines (BL-41, Ramos, CAPA-2) to TGF beta 1 in vitro.
- Assessment of apoptosis induction at 48 hours post-treatment.
- Analysis of c-myc and bcl-2 protein expression.
- Treatment with aphidicolin, a DNA synthesis inhibitor, for comparison.
- Evaluation of TGF beta 1 and aphidicolin effects on normal human tonsilar B cells and the CA46 BL cell line.
Main Results:
- TGF beta 1 induced apoptosis in EBV-negative lymphoma B cell lines (BL-41, Ramos, CAPA-2) within 48 hours.
- No significant apoptosis was observed in most normal human B cells (14/17 preparations) or the CA46 BL cell line.
- TGF beta 1 and aphidicolin inhibited DNA synthesis in both lymphoma and normal B cells.
- Apoptosis induction did not correlate with changes in c-myc and bcl-2 protein expression.
Conclusions:
- TGF beta 1-induced cell cycle arrest and DNA synthesis inhibition are not sufficient or obligatory for apoptosis induction.
- The induction or absence of apoptosis in response to TGF beta 1 appears to be determined by intrinsic cellular factors.
- These factors likely involve an interplay between extracellular and intracellular regulators governing cellular growth and survival.