Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.
Treatment of the Daudi Burkitt lymphomaderived cell line with human interferon a, which inhibits cell proliferation in this system, induces differentiation of these B-lymphoid cells into cells with a plasmacytoid phenotype. This differentiation, quantified by the appearance of surface antigens characteristic of mature plasma cells, is impaired by addition to the culture medium of the ADP-ribosyltransferase (ADPRT; EC 2.4.2.30) inhibitors 3-methoxybenzamide or 3-aminobenzamide. These agents also protect the cells against the inhibition of proliferation induced by low doses of interferon a. In contrast, the large inhibition of thymidine incorporation into DNA caused by interferon treatment is not affected by the ADPRT inhibitors. The phorbol ester phorbol 12-tetradecanoate 13-acetate induces the same plasma cell surface antigens that are induced by interferon treatment, and this effect is also impaired by the ADPRT inhibitors. These results suggest that interferons and phorbol esters share a mechanism of action that requires ADPRT activity. Protection of the cells against the antiproliferative effect of interferons by the ADPRT inhibitors suggests that growth inhibition may be a consequence of cell differentiation. In contrast, the inhibition of thymidine incorporation alone is not sufficient for the cessation of cell proliferation and is not a true reflection of the rate of DNA synthesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.