Anti‐proliferative effects of interferons on Daudiburkitt Lymphoma cells: Induction of cell differentiation and loss of response to autocrine growth factors

Abstract

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.

Latency Type-Dependent Modulation of Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Expression by Type I Interferons in B Cells

“…For initial experiments, we chose the highly IFN-␣-sensitive, EBV-positive BL line Daudi (29), in which IFN-␣ treatment inhibits cell proliferation and concomitantly induces plasmacytoid differentiation (8). Daudi cells were treated with different concentrations of IFN-␣, IFN-␤, and IFN-␥ (Peprotech) for 24 h, and the level of LMP-1 protein was analyzed by Western blotting (Fig.…”

Partial characterization of a cellular factor that regulates the double-stranded RNA-dependent eIF-2 alpha kinase in 3T3-F442A fibroblasts.

“…IFN has been reported to promote growth arrest and differentiation in some cells (10,33,38) and inhibit differentiation in others (16,42 (29,30). These observations, coupled with the findings of others, have led us to suggest that IFN has a regulatory role during the differentiation processes (29,30).…”

“…PIC (150 ng/ml) was added as indicated. Lanes 6 to 11 are phosphatase assays in which dsl was prephosphorylated for 10 kinase autophosphorylation and eIF-2ao phosphorylation are inhibited; however, if dRF is added to preactivated kinase (lane 9), dsl is not dephosphorylated, remains active, and is able to phosphorylate eIF-2o. These results indicate that the inhibition of dsl activity (eIF-2a phosphorylation) by dRF is a consequence of the inhibition of dsl activation (autophosphorylation).…”

“…Cessation of growth is thought to be a prerequisite for the transition from a proliferating fibroblast to a differentiated adipocyte (2,17,39). IFNs have been demonstrated to exert a diverse array of effects on many cellular processes in a number of different cells (6,8,28,40) and have been implicated in both the promotion (10,33,38) and inhibition (16,42) of cell differentiation.…”

Biochemical characterization of the membrane-associated phosphorylating proteins involved in the anti-proliferative effect of human recombinant interferon-alpha 2a (rIFN-.ALPHA.2a) in daudi cells.

“…An important biological property of interferons (IFNs) is their ability to inhibit the proliferation of many cell types in culture and in vivo (Hattori et al 1983 ; Clemens and Mcnurlan 1985 ;Exley 1987 et al). It has been clearly demonstrated that treatment of sensitive cells with IFNs alters the pattern of gene expression in many different cell types and brings about phenotypic changes (Weil et al 1983 ;Guardini et al 1984).…”