TRANSFORMING GROWTH-FACTOR-BETA-1 COOPERATES WITH ANTIIMMUNOGLOBULIN FOR THE INDUCTION OF APOPTOSIS IN GROUP-I (BIOPSY-LIKE) BURKITT-LYMPHOMA CELL-LINES
I. Macdonald et al., TRANSFORMING GROWTH-FACTOR-BETA-1 COOPERATES WITH ANTIIMMUNOGLOBULIN FOR THE INDUCTION OF APOPTOSIS IN GROUP-I (BIOPSY-LIKE) BURKITT-LYMPHOMA CELL-LINES, Blood, 87(3), 1996, pp. 1147-1154
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.