Production of growth factors by human myeloma cells

Using in vitro-growing myeloma cell lines, we studied the growth factors involved in human multiple myeloma, and particularly the potential of autocrine secretion and response to B-cell growth factor (BCGF) of RPMI 8226, the best-documented Epstein-Barr virus-negative human myeloma cell line. We found that three myeloma cell lines (RPMI 8226, U266, and IM9) produce an autostimulatory growth factor (AGF) and thus increase their own proliferation by 2- to 3-fold in cells cultured at low density. Optimal AGF production was obtained after 24 h of culture at a cell density ranging from 2.5 to 5 million cells/ml. The three myeloma cell lines produce type II BCGF, able to induce the proliferation of highly purified human peripheral blood B-cells, only after anti-mu activation. The BCGF produced by RPMI 8226 can be absorbed onto RPMI 8226 cells together with the RPMI 8226 AGF, and the two are copurified on gel filtration in a peak with an apparent molecular weight of 70,000. RPMI 8226 can be efficiently activated by human high molecular weight BCGF II (Mr 50,000) and less extensively by BCGF I (Mr 12,000). RPMI 8226 does not produce either detectable IL1 or interferons gamma and alpha and IL1 and gamma-IFN had no stimulating effect on RPMI 8226 proliferation. Our findings support the conclusion that RPMI 8226 produces a BCGF II working as an AGF.