Differences in the Behavior of the Membrane and Membrane-Associated Filamentous Structures in Normal and Chronic Lymphocytic Leukemia (CLL) Lymphocytes

Abstract

Ultrastructural studies of the membrane and membrane-associated cytoskeletal structures were carried out to help elucidate functional differences between normal and chronic lymphocytic leukemia (CLL) lymphocytes. A membrane-cross-linking ligand consisting of latex particles coated with anti-lymphocyte Ig permitted, because of its size, ultrastructural analysis of the site where the ligand had attached. In normal lymphocytes capped regions showed deep cytoplasmic invaginations and extensive polymerization of actin-like (7 nm) filaments in the adjacent submembranous zone. The presence of numerous bundles of intermediate filaments (10 nm) between the nucleus of the cell and the pole that carried the cap suggests a new role for these filaments in the capping process. CLL lymphocytes on the other hand showed deep cytoplasmic invaginations at sites of ligand binding over the entire cell surface. Actin-like filaments had also polymerized in the submembranous cytoplasm and had become attached to the plasma membrane by periodic cross bridges adjacent to these invaginations. However, organized arrays of intermediate (10 nm) filaments were not seen in CLL cells. Freeze-fracture studies after exposure of unfixed cells to glycerol revealed that the intramembranous particles (IMP) of normal lymphocytes had formed tight clusters whereas the IMP of CLL lymphocytes had either not been displaced at all or had formed only loose aggregates. This suggests the existence of a structural abnormality in the CLL Cell membrane that could interfere with IMP movement.