Loss of CD20 and Bound CD20 Antibody from Opsonized B Cells Occurs More Rapidly Because of Trogocytosis Mediated by Fc Receptor-Expressing Effector Cells Than Direct Internalization by the B Cells
| Autor: | Paul W. H. I. Parren, Ronald P. Taylor, Elizabeth M. Peek, Paul V. Beum, Frank J. Beurskens, Jan G. J. van de Winkel, Margaret A. Lindorfer, Patrick J. Engelberts |
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| Přispěvatelé: | University of Groningen |
| Rok vydání: | 2011 |
| Předmět: |
Trogocytosis
media_common.quotation_subject Chronic lymphocytic leukemia ANTIGEN Immunology Fc receptor Antineoplastic Agents Cell Separation Biology Transfection Ofatumumab THERAPY Monocytes MECHANISMS Cell Line Antibodies Monoclonal Murine-Derived Mice chemistry.chemical_compound Immune system immune system diseases hemic and lymphatic diseases medicine Animals Humans Immunology and Allergy NON-HODGKINS-LYMPHOMA MODULATION ANTI-CD20 MONOCLONAL-ANTIBODIES Internalization media_common CD20 B-Lymphocytes integumentary system CHRONIC LYMPHOCYTIC-LEUKEMIA Receptors IgG Antigens CD20 Flow Cytometry medicine.disease Leukemia Lymphocytic Chronic B-Cell Molecular biology Endocytosis chemistry biology.protein Antibody COMPLEMENT ACTIVATION Rituximab |
| Zdroj: | Journal of Immunology, 187(6), 3438-3447. AMER ASSOC IMMUNOLOGISTS |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | We previously reported that 1 h after infusion of CD20 mAb rituximab in patients with chronic lymphocytic leukemia (CLL), >80% of CD20 was removed from circulating B cells, and we replicated this finding, based on in vitro models. This reaction occurs via an endocytic process called shaving/trogocytosis, mediated by FcγR on acceptor cells including monocytes/macrophages, which remove and internalize rituximab–CD20 immune complexes from B cells. Beers et al. reported that CD20 mAb-induced antigenic modulation occurs as a result of internalization of B cell-bound mAb–CD20 complexes by the B cells themselves, with internalization of ∼40% observed after 2 h at 37°C. These findings raise fundamental questions regarding the relative importance of shaving versus internalization in promoting CD20 loss and have substantial implications for the design of mAb-based cancer therapies. Therefore, we performed direct comparisons, based on flow cytometry, to determine the relative rates and extent of shaving versus internalization. B cells, from cell lines, from patients with CLL, and from normal donors, were opsonized with CD20 mAbs rituximab or ofatumumab and incubated for varying times and then reacted with acceptor THP-1 monocytes to promote shaving. We find that shaving induces considerably greater loss of CD20 and bound mAb from opsonized B cells in much shorter time periods (75–90% in |
| Databáze: | OpenAIRE |
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