TRANSFORMING GROWTH-FACTOR-BETA-1 COOPERATES WITH ANTIIMMUNOGLOBULIN FOR THE INDUCTION OF APOPTOSIS IN GROUP-I (BIOPSY-LIKE) BURKITT-LYMPHOMA CELL-LINES

Group I Burkitt lymphoma (BL) cell lines, which retain the original bi opsy phenotype, have been shown to enter apoptosis in response to a nu mber of external stimuli including serum deprivation, thermal shock, a ddition of calcium ionophore, and ligation of surface immunoglobulin ( Ig) by antibody. Transforming growth factor-beta 1 (IGF beta 1) is kno wn to cause growth arrest in BL lines. Here we show that while it is b y itself capable of promoting some degree of apoptosis in group I BL c ells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trim eric soluble recombinant human CD40 ligand (sCD40L) was able to inhibi t apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-IG ind ividually caused BL cells to undergo growth arrest at the G(1) phase o f cell cycle before their entry into apoptosis: the consequence of sCD 40L. addition was to maintain the cells in cycle for longer. No induct ion of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promot ing apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma . (C) 1996 by The American Society of Hematology.