Dynamics of Macrophage Trogocytosis of Rituximab-Coated B Cells
Open accessAbstract
Macrophages can remove antigen from the surface of antibody-coated cells by a process termed trogocytosis. Using live cell microscopy and flow cytometry, we investigated the dynamics of trogocytosis by RAW264.7 macrophages of Ramos B cells opsonized with the anti-CD20 monoclonal antibody rituximab. Spontaneous and reversible formation of uropods was observed on Ramos cells, and these showed a strong enrichment in rituximab binding. RAW-Ramos conjugate interfaces were highly enriched in rituximab, and transfer of rituximab to the RAW cells in submicron-sized puncta occurred shortly after cell contact. Membrane from the target cells was concomitantly transferred along with rituximab to a variable extent. We established a flow cytometry-based approach to follow the kinetics of transfer and internalization of rituximab. Disruption of actin polymerization nearly eliminated transfer, while blocking phosphatidylinositol 3-kinase activity only resulted in a delay in its acquisition. Inhibition of Src family kinase activity both slowed acquisition and reduced the extent of trogocytosis. The effects of inhibiting these kinases are likely due to their role in efficient formation of cell-cell conjugates. Selective pre-treatment of Ramos cells with phenylarsine oxide blocked uropod formation, reduced enrichment of rituximab at cell-cell interfaces, and reduced the efficiency of trogocytic transfer of rituximab. Our findings highlight that dynamic changes in target cell shape and surface distribution of antigen may significantly influence the progression and extent of trogocytosis. Understanding the mechanistic determinants of macrophage trogocytosis will be important for optimal design of antibody therapies.
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Trogocytosis is a non-apoptotic mechanism for rapid capture of membrane components and differs from phagocytosis, which involves engulfment and elimination of larger cellular structures (>1 μm).
“Trogocytosis has been described in the immune system as a non-apoptotic mechanism for the rapid capture of membrane components and differs from phagocytosis, which involves the engulfment and elimination of larger cellular structures (> 1 µm)17–19.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [18]
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Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Weinhard, L., di Bartolomei, G., Bolasco, G., Machado, P., Schieber, N. L., Neniskyte, U., Exiga, M., Vadisiute, A., Raggioli, A., Schertel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03566-5 · Cited by 790 · see citing works
- Authors
- Pham, T., Mero, P., & Booth, J. W.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Booth, James W.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-01-17
- Volume
- 6
- Issue
- 1
- Pages
- e14498
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3022012
- OpenAlex
- W2049456898
- Cited by
- 66
- References
- 33
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Sunnybrook Research Institute
- University of Toronto
- Canadian Institutes of Health Research (MOP84475)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- trogocytosis, macrophages, rituximab, B cells, opsonization, anti-CD20 monoclonal antibody, uropod, antibody internalization, actin polymerization, phosphatidylinositol 3-kinase, Src family kinases, phenylarsine oxide, RAW 264.7 macrophages, Ramos cells
- MeSH terms
- Rituximab, Animals, B-Lymphocytes, Cell Line, Flow Cytometry, Kinetics, Macrophages, Opsonin Proteins, Antigens, CD20, Cell Shape, Mice, Antibodies, Monoclonal, Murine-Derived
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