Glycosphingolipid Domain Formation and Lymphoid Cell Activation

Abstract

Peripheral blood lymphocytes are stimulated to mitosis following interaction of plasma membrane receptors with a wide range of ligands, including the seed-derived lectins, phytohaemagglutinin (PHA) and concanavalin-A (Con-A). A series of biochemical events follow ligand binding, including an influx of Ca⁺⁺ into the cell (Allwood et al 1971), an increased uptake of metabolites (Greaves and Janossy, 1972), increased synthesis of cyclic nucleotides (Edelman, 1974), increased turnover of phosphatidyl inositol and increased RNA and DNA and protein synthesis, culminating in mitosis (Diamenstein and Ulmer, 1975; Whitney and Sutherland, 1972; Alford, 1970). Ligand-induced receptor clustering (“patching and capping”) is one of the earliest observable phenomena following ligand binding. Spin label and immunofluorescence studies have shown that patching is accompanied by clustering of glycosphingolipids (Curtain et al 1978; Curtain, 1979). The immunofluorescence studies were done by making fluorescein-labelled antibodies to cerebroside or gangliosides and using these to counterstain B-lymphocytes which had been patched or capped with rhodamine-labelled anti-immunoglobulin antiserum.