Globotriaosyl ceramide modulates interferon-alpha-induced growth inhibition and CD19 expression in Burkitt's lymphoma cells

Previous studies have indicated that globotriaosyl ceramide (Gb3 or CD77) p lays a role in alpha -interferon signal transduction and CD19-mediated homo typic adhesion in B cell lines derived from Burkitt's lymphoma. These roles for Gb3 may involve the proteins IFNAR-1 (subunit 1 of the interferon-alph a receptor) and CD19, respectively, both of which have potential Gb3-bindin g sites in their extracellular domains which resemble those of the verotoxi n (Shiga toxin and Shiga-like toxin) B subunit. The majority of this work w as performed using wild-type Daudi cells and a single, Gb3-deficient mutant cell line, VT500. In the present investigations, these and additional Daud i-derived cells with varying degrees of sensitivity to interferon-alpha wer e examined for Gb3 expression, interferon-induced growth inhibition and CD1 9 expression. The degree of interferon-induced growth inhibition and CD19 e xpression correlated with Gb3 expression in the various cell lines tested. In addition, reconstitution of the VT500 cell line with Gb3 but not other g lycolipids partially restored the sensitivity of cells to IFN-induced growt h inhibition. The degree to which reconstitution restored sensitivity to gr owth inhibition was similar to the results of previous studies in which Gb3 reconstitution restored sensitivity to verotoxin-induced cytotoxicity. The se results demonstrate that Gb3 is specifically required for IFN-induced gr owth inhibition in Daudi cells and provide further evidence of a role for G b3 in CD19 expression and function in these cells.