THE ROLE OF BCL-2 PROTEIN AND AUTOCRINE GROWTH-FACTORS IN A HUMAN FOLLICULAR LYMPHOMA-DERIVED B-CELL LINE

We have shown that the ability of the human follicular lymphoma-derive d cell line SU-DHL-6 to proliferate and survive in vitro depends on bo th Bcl-2 expression and multiple autocrine growth factors. Treatment w ith Bcl-2 antisense (AS Bcl-2) decreased Bcl-2 protein levels, However , a cytotoxic effect was seen only at very restricted cell densities. Below such densities cells underwent spontaneous death without any tre atment, while above these cell densities no cytotoxic effect of AS Bcl -2 could be seen. The conditioned medium of SU-DHL cells supported the survival and growth of these cells cultivated at low cell densities a nd partially reversed the cytotoxicity associated with Bcl-2 depletion , RT/PCR analysis revealed autocrine expression of IL-1 beta, IL-2, IL -5 and TNF-beta in SU-DHL cells. Neutralizing antibodies against these cytokines inhibited SU-DHL proliferation, Thus, development of autocr ine GF secretion may be the second step in the pathogenesis of follicu lar lymphomas,