Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human malignant B cells

Abstract

Antibody-induced antigenic modulation (AIAM) is a complex biological phenomenon closely resembling other receptor-ligand interactions. Following exposure to specific antibodies, surface antigens are usually rapidly redistributed on the cell surface and internalized. A subsequent intracellular processing results in dissociation of the antigen-antibody complexes, degradation, exocytosis and recycling. AIAM plays an important role in MoAb-targeted therapy of hematopoietic malignancies contributing to escape of tumor cells from immunodestruction. On the other hand, internalization of MoAbs used as carriers of toxins and drugs is a prerequisite of therapeutic efficacy. Even though MoAbs directed against CD10 and CD19 have been used in immunotherapy of B cell malignancies, some aspects regarding AIAM of these Ags are not yet fully understood. Both Ags are modulated by specific MoAbs and internalized through the same pathway, however, the kinetics of AIAM vary from one Ag to another and from one cell type to another. Recent studies with malignant B-cell lines show that, under certain experimental conditions, the extent and rate of surface clearing, uptake and intracellular transport are considerably higher in the case of CD19 than in CD10 and higher in less mature cells compared with more mature cells. These observations may be useful in the selection of MoAbs for immunotherapy, although they need to be confirmed with fresh malignant B cells.