Characterization of transforming growth factor-β1 induced apoptosis in normal human B cells and lymphoma B cell lines

Transforming growth factor β1 (TGFβ1) 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 TGFβ1, undergo apoptosis. Maximum apoptosis was observed at 48 h following TGFβ1 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 TGFβ1 and aphidicolin inhibited anti-μ/IL-4 induced DNA synthesis in all preparations. Furthermore, another TGFβ1 sensitive EBV-negative BL cell line, CA46, exhibited no apoptosis in response to TGFβ1 and aphidicolin, corroborating the findings in normal human B cells. Taken together, these data support the hypothesis that exposure to TGFβ1, 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.