DIFFERENTIAL ADHESION PATTERN OF B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS

Binding of B cell chronic lymphocytic leukemia (B-CLL) cells to other cells and to extracellular matrices influences the pathophysiology and the clinical presentation of the B-CLL disease. It is still unknown w hich adhesion pathways regulate the traffic of B-CLL cells within dist inct histologic compartments of lymphoid organs. In addition, it is no t yet clarified which mechanisms mediate the intercellular adhesion of B-CLL cells. The present study sought to identify the mechanisms that are involved in the binding of B-CLL cells to secondary lymphoid orga ns in situ and in the homotypic aggregation of these cells. B-CLL cell s specifically bound to germinal centers of normal human tonsils via t he adhesion pair integrin alpha 4 beta 1/vascular cell adhesion molecu le-1 (VCAM-1). Among a large panel of antibodies tested only mAbs agai nst CD19 induced homotypic adhesion of B-CLL cells via the adhesion mo lecules integrin alpha(L) (leukocyte function antigen-1 (LFA-1)), inte rcellular adhesion molecule-1 (ICAM-1) and CD21. Anti-CD19-induced agg regation required protein synthesis. We hypothesize that the observed heterotypic and homotypic adhesion of B-CLL cells reflects the ability of these leukemic cells to migrate in vivo.