IL-6 IS AN AUTOCRINE GROWTH FACTOR FOR EBV IMMORTALIZED B CELLS

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Epstein-Barr virus (EBV) is an immortalizing herpesvirus for human B lymphocytes. The mechanisms responsible for EBV induction and maintenance of an immortalized state in B cells are presently unknown. Recent evidence, however, has suggested that EBV-immortalized B cells produce growth factor activities in the supernatant and then use them to sustain proliferation. Thus, it was suggested that the establishment of an autocrine loop might be an essential feature of B cell immortalization by EBV. A number of molecules have been proposed as being responsible for autocrine growth stimulation in EBV-immortalized B cells, including soluble CD 23 and a newly identified polypeptide with IL-1 bioactivity. In the present study, we have identified Interleukin-6, IL-6, as an autocrine growth factor for EBV-infected B cells. All lymphoblastoid cell lines tested (no 12) produced IL-6 bioactivity in variable amounts (0.5-50 U/ml 72 hr), as measured in a standard B9 assay. In addition, IL-6 could be immunoprecipitated from 35-S-labelled supernatants of all EBV-immortalized cell lines tested, using a heteroantiserum to human IL-6. When IL6 was partially purified from the culture supernatant of a lymphoblastoid cell line and separated from other growth factor activities also present, it acted as an autocrine growth factor for the cells producing it, and this activity was neutralized both by a monoclonal as well as by a polyclonal antibody to human IL-6. Thus, we have identified IL-6 as an autocrine growth factor for EBV-immortalized B cells.