ArticleThe Journal of biological chemistry2015
Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation.The EMBO journal · 2026Article
- Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity.Science advances · 2025Article
- The ETS-family transcription factor PU.1 is a critical regulator of the inhibitory Fcγ receptor IIB expression in humans.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- Antibody surface mobility amplifies FcγR signaling via Arp2/3 during phagocytosis.Biophysical journal · 2024Article
- Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML.Antibody therapeutics · 2024Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- AL008 Enhances Myeloid Antitumor Function by Inhibiting SIRPα Signaling and Activating Fc Receptors.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- FcγRIIB controls antibody-mediated target cell depletion by ITIM-independent mechanisms.Cell reports · 2022Article
- STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.Clinical and experimental immunology · 2020Article
- Monitoring of the Complement System Status in Patients With B-Cell Malignancies Treated With Rituximab.Frontiers in immunology · 2020Article
- Complement-Dependent Activity of CD20-Specific IgG Correlates With Bivalent Antigen Binding and C1q Binding Strength.Frontiers in immunology · 2020Article
- The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease.Frontiers in immunology · 2019Review
- Detection of Experimental and Clinical Immune Complexes by Measuring SHIP-1 Recruitment to the Inhibitory FcγRIIB.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Activating Autophagy Enhanced the Antitumor Effect of Antibody Drug Conjugates Rituximab-Monomethyl Auristatin E.Frontiers in immunology · 2018Article
- IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.Nature immunology · 2017Article
- Regulation of Monoclonal Antibody Immunotherapy by FcγRIIB.Journal of clinical immunology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.