Abstract
We demonstrate herein the augmentation of rituximab-mediated apoptosis in lymphoma cell lines by cross-linking with recombinant FcgammaRs, which is further enhanced by using a nonfucosylated variant of rituximab having strong FcgammaRIII-binding capacity. Furthermore, we show that neutrophils can serve as physiological cross-linkers that augment anti-CD20-mediated apoptosis, as evidenced by (i) the neutrophil-augmented apoptosis was more profound for the nonfucosylated variant of rituximab and (ii) the mechanism depended on FcgammaRIIIb but not on FcgammaRIIa. Taken together, we suggest a potential anti-tumour mechanism of nonfucosylated anti-CD20 antibody by which antibody molecules are cross-linked through enhanced interaction with FcgammaRIIIb in neutrophils.