Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas

Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells^1,2. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (M_r) 26,000 similar or identical to interferon β₂, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor^3-7. IL-6 has been proposed as a name for this molecule^8,9. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells^1,10. Responses are also seen in T cells^11,12, plasmacytomas⁶, hepatocytes^7,13, haematopoietic stem cells¹⁴, fibroblasts¹⁵ and rat phoeochromocytoma, PC 12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas^6,8,10. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.