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 glycoconjugates, plays an important role in a variety of biological processes. In this study, we investigated subclones of the human B lymphoma cell line BJA-B for differences in the glycosylation of cell surface glycoconjugates, and studied the functional implications of such differences. With respect to the expression 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 sialylation, involving both alpha-2,6 and alpha-2,3-linked sialic acid residues. Accordingly, subclones were classified as highly- (group I) or hyposialylated (group II). The function of two sialic acid-dependent receptor-mediated processes is correlated with the sialylation status of BJA-B subclones. Susceptibility to and binding of the B lymphotropic papovavirus (LPV) was dependent on a high sialylation status of host cells, suggesting that differential sialylation in BJA-B cells can modulate LPV infection via its alpha-2,6-sialylated glycoprotein receptor. CD95-mediated apoptosis, induced by either the human CD95 ligand or a cytotoxic anti-CD95 monoclonal antibody, was drastically enhanced in hyposialylated group II cells. An increase in endogenous sialylation may be one antiapoptotic mechanism that converts tumor cells to a more malignant phenotype. To our knowledge, this is the first report demonstrating that differential sialylation in a clonal cell line may regulate the function of virus and signal-transducing receptors.
Keppler
O T
OT
Angewandte Tumorvirologie and Tumorimmunologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Peter
M E
ME
Hinderlich
S
S
Moldenhauer
G
G
Stehling
P
P
Schmitz
I
I
Schwartz-Albiez
R
R
Reutter
W
W
Pawlita
M
M
D002241:Carbohydrates / Q000737:chemistry; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002999:Clone Cells; D015180:Electrophoresis, Gel, Two-Dimensional; D006001:Glycoconjugates / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D027382:Polyomaviridae; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D002241:Carbohydrates; D006001:Glycoconjugates; D019014:fas Receptor; D019158:N-Acetylneuraminic Acid