INCREASED INHIBITION OF PROLIFERATION OF HUMAN B-CELL LYMPHOMAS FOLLOWING LIGATION OF CD40, AND EITHER CD19, CD20, CD95 OR SURFACE-IMMUNOGLOBULIN

Non-Hodgkin's (NHL) B cell lymphomas are growth-inhibited by ligation of their CD40 molecules. This inhibition is not absolute in that appro ximate to 50% of the cells are not inhibited. We conducted studies to see if other signals that have been reported to inhibit B cell lymphom a growth could be used in combination with anti-CD40 signaling to comp letely inhibit growth. Ligation of surface immunoglobulin (Ig), CD19, CD20, CD37 or CD95 with soluble antibody did not affect growth of the panel of NHL cells examined. Ligation of CD20, CD19 or CD95 was inhibi tory for some NHL cell lines if the primary antibody was crosslinked w ith a secondary antibody. Combining anti-CD40 with anti-CD19, anti-CD2 0, or anti-Ig resulted in increased inhibition past that produced by a nti-CD40 alone. The additive effect of anti-CD40 and other antibodies to selected surface markers was not observed in all NHL, cell lines. C rosslinking of CD95 was also growth inhibitory for the majority of the NHL, and when combined with anti-CD40 under conditions that afforded crosslinking of the two receptors, increased inhibition was seen in th ree of the NHL cell lines. We found that cAMP or sodium butyrate (NaB) were also effective at inhibiting growth of the NHL cells; this was a profound inhibition (approaching 100%) compared to the 50% inhibition seen with anti-CD40 treatment. The potential for anti-CD40 and either cAMP or NaB to be additive was tested and not found to be the case. T he ability to inhibit proliferation of the NHL was very dynamic with s ome antibody combinations being either inhibitory for multiple cells, not having an effect at all, or in some cases being stimulatory. This suggests that the NHL may represent unique stages of B cells that migh t serve as a model system which could be developed to precisely catego rize patient NHL.