HUMAN-CHROMOSOME-21 DETERMINES GROWTH-FACTOR DEPENDENCE IN HUMAN MOUSE B-CELL HYBRIDOMAS/

Interleukin 6 (IL-6) serves as a growth factor for mouse plasmacytomas . As a model for IL-6-mediated growth of plasmacytomas, we study IL-6- dependent B-cell hybridomas, which can be generated through fusion of B lymphocytes with a plasmacytoma cell line, e.g., SP2/0. In the prese nt report, we have investigated the peculiar behavior of B-cell hybrid omas with respect to IL-6 dependence. We demonstrate that although new ly generated hybridomas are IL-6 dependent, many hybridomas lose this dependency at frequencies as high as 50%, shortly after fusion. We spe culated that the loss of IL-6-dependent growth is due to the well-know n chromosomal instability of B-cell hybridomas. Consequently, Loss of IL-6 dependence is the result of loss of a specific chromosome(s). Thi s model implies the existence of an ''IL-6 dependency'' gene, the loss of which makes hybridomas capable of proliferating in the absence of IL-6. Because SP2/0 is IL-6 independent, the IL-6-dependent phenotype of B-cell hybridomas, and hence the IL-6 dependency gene, must be deri ved from the B lymphocyte. We have tested this model by generating hum an/mouse B-cell hybridomas through fusion of human B lymphocytes with SP2/0. We then analyzed the human chromosome content of 10 IL-6-depend ent and 14 IL-6-independent subclones. From that analysis we concluded that the presence of human chromosome 21 correlated with IL-6 depende nce. This correlation was confirmed by microcell fusion experiments in which a single copy of chromosome 21 was introduced into IL-6-indepen dent hybridomas, resulting in reconstitution of the IL-6-dependent phe notype. We therefore conclude that chromosome 21 carries an IL-6 depen dency gene.