Monoclonal Lym-1 antibody-dependent cytolysis by neutrophils exposed to granulocyte-macrophage colony-stimulating factor: Intervention of Fc gamma R-II(CD32), CD11b-CD18 integrins, and CD66b glycoproteins

Murine monoclonal antibody (MoAb) Lym-1 is an IgG2a able to bind HLA-DR var iants on malignant B cells and suitable far serotherapeutic approaches in B -lymphoma patients. We have previously shown that Lym-1 can synergize with granulocyte-macrophage colony-stimulating factor (GM-CSF) to trigger neutro phil cytolysis towards Raji cells used as a model of B-lymphoma targets. He re we provide evidence for the intervention of certain neutrophil receptors or surface molecules in this model of cell-mediated lysis, The lysis was c ompletely inhibited by the anti-Fc gamma R-II MoAb IV.3 and unaffected by t he anti-Fc gamma R-III MoAb 3G8, This suggests that neutrophil cytolysis in volves Fc gamma R-II without cooperation of this receptor with Fc gamma R-I II. Moreover, the lysis was inhibited by an anti-CD18 MoAb (MEM48) and by a MoAb specific for carcinoembryonic antigen (CEA)-like and glycophosphatidy l inositol (GPI)-linked glycoproteins (CD66b). Using an immunofluorescence staining procedure, cross-linking of CD66b induced the redistribution of CD 11b on neutrophils with distinct areas of CD11b clustering via a process su sceptible of inhibition by D-mannose. This is consistent with the ability o f CD11b-CD18 and CD66b to undergo lectin-like physical interactions on the neutrophil surface. Such a type of interaction is presumably instrumental f or neutrophil cytolytic activity in that the lysis was inhibited by D-manno se and enhanced by the MoAb VIM-12, which mimics the cooperation between CD 11b and GPI-anchored molecules by specifically interacting with CD11b lecti n-like sites. Therefore, the present results prove the absolute requirement for Fc gamma R-II in neutrophil GM-CSF/Lym-1-mediated cytolysis and, on th e other hand, define the crucial role of CD66b and CD11b/CD18 in the expres sion of the cell lytic potential. (C) 1999 by The American Society of Hemat ology.