Signal transduction initiated by binding of antibodis to cell surface molecules can have an important impact on the growth of tumor cells. (8), the effectiveness of anti-CD19 antibodies in preventing tumor growth probably results from a signal transduction phenomenon similar to that observed for anti-immunoglobulin (antiIg) on BCL1, rather than a classical antibody-mediated effector function, e.g., antibody-dependent cellular cytotoxicity.Here we show that anti-Ig induces an antiproliferative response in a subclone of BCL1, BCL1.3B3 (9), that includes the induction of cell cycle arrest and apoptosis. Treatment of BCL1.3B3 cells with specific antisense oligonucleotides results in the depletion of the Lyn tyrosine kinase protein.When depleted cells are challenged with anti-Ig, apoptosis is still induced, but cell cycle arrest is not. The same result is observed in anti-Ig-treated Daudi lymphoma cells. In addition, antisense lyn can prevent cell cycle arrest induced by the cross-linking ofCD19. These results indicate that the Lyn tyrosine kinase is required for transduction of the cell cycle arrest signal initiated by cross-linking of mlg or CD19.
MATERIALS AND METHODSAntibodies and Antsens Olguclides. BCL1.3B3 cells were cultured in RPMI 1640 medium with 5% (vol/vol) fetal calf serum. Antibody preparations (7,8,10,11) were affinitypurified and included rabbit anti-ovalbumin (35 pg/ml), rabbit anti-BCL, idiotype (35 pg/ml), goat anti-human IgM (7.5 pg/ml), goat anti-ovalbumin (7.5 mg/ml), and anti-CD19 (HD37; 350 pg/ml).Cells were plated with antisense oligonucleotides 24 hr before the addition of antibody. Oligonucleotides were phosphorothioate derivatives synthesized by Oligos Etc. (Guilford, CT). For the BCL,.3B3-cell experiments, the sequences TG-