Induction of surface marker changes and monoclonal idiotypic immunoglobulin secretion in lymphoma/leukemia cells: comparative study with interleukin-1, interleukin-2, interleukin-4, 8-bromo-guanosine, pokeweed mitogen, and tetradecanoyl phorbol-13-acetate.
Induction of differentiation in B lymphoma/leukemia cells with interleukins was compared with differentiation induced by phorbol ester (TPA) and pokeweed mitogen (PWM) or by 8-bromo-guanosine. Both cell surface changes and monoclonal immunoglobulin (Ig) secretion were followed as markers of differentiation. The results indicate great similarity in the differentiation patterns induced by interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-4 (IL-4), with regard to Ig secretion and changes in surface markers. Induction of Ig secretion and surface marker changes by 8-bromo-guanosine was similar to that induced by TPA and PWM; however, for some markers, cell surface changes induced by TPA and PWM or by 8-bromo-guanosine were quite different from those induced by the three interleukins tested. Whereas all three interleukins stimulated the expression of CD5, PWM and TPA and 8-bromo-guanosine substantially decreased CD5 expression on B lymphoma cells. Differences were also observed in the effect on the expression of surface Ig and on the expression of CD19 and CD20. Interestingly, the three interleukins tested and 8-bromo-guanosine induced differentiation and Ig secretion within 24 to 48 hours with no prior activation by B-cell activators, such as anti-surface Ig antibody. These results suggest that leukemic B cells are arrested at a point distal to activation and first cell division. Moreover, the similarity in Ig secretion and surface changes induced by TPA and PWM or 8-bromo-guanosine suggest a similar pathway; however, this pathway is different from the differentiation signal induced by the three interleukins.
Gazitt
Y
Y
Department of Pediatrics, College of Medicine, Gainesville, FL 32610.
Gangavalli
A
A
Thurman
G B
GB
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000954:Antigens, Surface; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007130:Immunoglobulin Idiotypes; D007378:Interleukins; D011043:Pokeweed Mitogens; D006151:Guanosine; C035169:8-bromoguanosine; D013755:Tetradecanoylphorbol Acetate