Transforming growth factor-beta 1 cooperates with anti-immunoglobulin 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 biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit 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 individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction 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 promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.
MacDonald
I
I
Department of Immunology, Medical School, Birmingham, UK.
Wang
H
H
Grand
R
R
Armitage
R J
RJ
Fanslow
W C
WC
Gregory
C D
CD
Gordon
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D002051:Burkitt Lymphoma / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D023201:CD40 Ligand; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C044203:anti-IgM; D023201:CD40 Ligand