Monoclonal Lym-1 antibody-targeted lysis of B lymphoma cells by neutrophils. Evidence for two mechanisms of FcγRII-dependent cytolysis

Human neutrophils incubated with the anti‐HLA‐DR mAb Lym‐1, plus PMA, induced significant cytolysis of B lymphoma cells compared with Lym‐1 and PMA alone. The effect of PMA was independent of the ability of the compound to stimulate neutrophil‐respiratory burst. In fact, first, neutrophils from a patient with chronic granulomatous disease were cytolytically effective in spite of their inability to produce oxidants. Second, various kinase inhibitors exerted different effects on the PMA‐stimulated cytolytic system and neutrophil‐oxidative burst. Previous studies have shown the involvement of the FcγRII, CD11b‐CD18 integrins, and CD66b glycoproteins in the Lym‐1 mAb‐dependent cytolysis by GM‐CSF‐stimulated neutrophils. The present PMA‐stimulated system was inhibited by the anti‐FcγRII mAb IV.3, the anti‐CD18 mAb MEM 48, and the anti‐CD11b mAb 2LPM19c but not by the anti‐CD66b mAb 80H3 andN‐acetyl‐d‐glucosamine. Furthermore, the PMA‐ and GM‐CSF‐stimulated cytolysis was insensitive and sensitive to inhibition by pertussis toxin, respectively. Thus, the use of PMA and GM‐CSF as neutrophil stimulants uncovers the existence of distinct mechanisms of Lym‐1 mAb‐mediated cytolysis.