ArticleJournal of immunology (Baltimore, Md. : 1950)2011
TOSO, the Fcmicro receptor, is highly expressed on chronic lymphocytic leukemia B cells, internalizes upon IgM binding, shuttles to the lysosome, and is downregulated in response to TLR activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Pooled it
- The risk of reactivity against healthy tissues: Novel CARs demand testing for overlooked binding properties.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lysosome targeted therapies in hematological malignancies.Frontiers in oncology · 2025Review
- Structural basis for Fc receptor recognition of immunoglobulin M.Nature structural & molecular biology · 2023Article
- Physiological and Pathophysiological Roles of IgM Fc Receptor (FcµR) Isoforms.International journal of molecular sciences · 2023Review
- Immunoglobulin M perception by FcμR.Nature · 2023Article
- Chimeric Antigen Receptor T-cell Therapy for Chronic Lymphocytic Leukemia: What is the supporting evidence so far?Clinical hematology international · 2023Review
- Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2022Review
- Reply to: Questioning whether the IgM Fc receptor (FcμR) is expressed by innate immune cells.Nature communications · 2022Article
- An Unexpected Role for Cell Density Rather than IgM in Cell-Surface Display of the Fc Receptor for IgM on Human Lymphocytes.ImmunoHorizons · 2022Article
- Soluble Fc Receptor for IgM in Sera From Subsets of Patients With Chronic Lymphocytic Leukemia as Determined by a New Mouse Monoclonal Antibody.Frontiers in immunology · 2022Article
- Identification of increased expression of activating Fc receptors and novel findings regarding distinct IgE and IgM receptors in Kawasaki disease.Pediatric research · 2021Article
- Generation of oligomers of subunit vaccine candidate glycoprotein D of Herpes Simplex Virus-2 expressed in fusion with IgM Fc domain(s) in3 Biotech · 2020Article
- Structure, Function, and Therapeutic Use of IgM Antibodies.Antibodies (Basel, Switzerland) · 2020Review
- Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type.Cancers · 2020Article
- Mapping of the binding site for FcμR in human IgM-Fc.Biochimica et biophysica acta. Proteins and proteomics · 2020Article
- Secreted IgM: New tricks for an old molecule.Journal of leukocyte biology · 2019Review
- Functional Roles of the IgM Fc Receptor in the Immune System.Frontiers in immunology · 2019Review
- Role of the IgM Fc Receptor in Immunity and Tolerance.Frontiers in immunology · 2019Review
- Surface receptor Toso controls B cell-mediated regulation of T cell immunity.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
TOSO/FAIM3 recently has been identified as the long-sought-after FcR for IgM (FcμR). FcμR is expressed on human CD19(+) B cells, CD4(+)/CD8(+) T cells, and CD56(+)/CD3(-) NK cells and has been shown to be overexpressed in chronic lymphocytic leukemia (CLL) cells. CLL is a malignancy of mature IgM(+) B lymphocytes that display features of polyreactive, partially anergized B cells related to memory B cells. In this article, we report that FcμR is O-glycosylated in its extracellular domain and identify the major sites of O-glycosylation. By using immunofluorescence confocal microscopy, we found that FcμR localized to the cell membrane but also found that large pools of FcμR accumulate in the trans-Golgi network. Aggregation of FcμR on CLL cells by IgM prompted rapid internalization of both IgM and FcμR, reaching half-maximal internalization of cell-bound IgM within 1 min. Upon internalization, FcμR transported IgM through the endocytic pathway to the lysosome, where it was degraded. Using a series of FcμR deletion mutants, we identified a proline-rich domain essential for cell surface expression of FcμR and a second domain, containing a YXXΦ motif, that controls internalization. Although it has been reported that BCR activation increases FcμR expression, we found that activation of TLRs strongly downregulated FcμR at both the mRNA and protein levels. Through internalization of IgM bound immune complexes, FcμR may play a role in immune surveillance and contribute to B cell activation. In addition, FcμR deserves study as a potential pathway for the delivery of therapeutic Ab-drug conjugates into CLL cells.
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Registered trials
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.