Differential sialylation of cell surface glycoconjugates in a human B lymphoma cell line regulates susceptibility for CD95 (APO-1/Fas)-mediated apoptosis and for infection by a lymphotropic virus

Sialic acid, as a terminal saccharide residue on cell surface glycoconjugat es, plays an important role in a variety of biological processes. In this s tudy, me investigated subclones of the human B lymphoma cell line BJA-B for differences in the glycosylation of cell surface glycoconjugates, and stud ied the functional implications of such differences. With respect to the ex pression level of most of the tested B cell-associated antigens, as well as the presence of penultimate saccharide moieties on oligosaccharide chains, subclones were phenotypically indistinguishable. Marked differences among subclones, however, were found in the overall level of glycoconjugate sialy lation, involving both alpha-2,6 and alpha-2,3-linked sialic acid residues. Accordingly, subclones were classified as highly- (group I) or hyposialyla ted (group II). The function of two sialic acid-dependent receptor-mediated processes is correlated with the sialylation status of BJA-B subclones. Su sceptibility to and binding of the B lymphotropic papovavirus (LPV) was dep endent on a high sialylation status of host cells, suggesting that differen tial sialylation in BJA-B cells can modulate LPV infection via its alpha-2, 6-sialylated glycoprotein receptor, CD95-mediated apoptosis, induced by eit her the human CD95 ligand or a cytotoxic anti-CD95 monoclonal antibody, was drastically enhanced in hyposialylated group II cells. An increase in endo genous sialylation may be one anti-apoptotic mechanism that converts tumor cells to a more malignant phenotype, To our knowledge, this is the first re port demonstrating that differential sialylation in a clonal cell line may regulate the function of virus and signal-transducing receptors.