ArticlePloS one2013
Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Inhibition of autoantigen-induced B-cell receptor (BCR) internalization as a therapeutic strategy in diffuse large B cell lymphoma (DLBCL).Cell death & disease · 2026Article
- Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions.Cellular & molecular immunology · 2025Article
- Heterogeneous Surface CD79b Expression in Aggressive B-Cell Lymphomas Assessed by Flow Cytometry on Lymph Node Biopsies.Cancers · 2024Article
- Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.ImmunoHorizons · 2024Article
- B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells.International journal of molecular sciences · 2023Review
- NF-kB's contribution to B cell fate decisions.Frontiers in immunology · 2023Review
- B cell receptor (BCR) endocytosis.Progress in molecular biology and translational science · 2023Review
- NF-κB Mutations in Germinal Center B-Cell Lymphomas: Relation to NF-κB Function in Normal B Cells.Biomedicines · 2022Review
- Characterization of interactions within the Igα/Igβ transmembrane domains of the human B-cell receptor provides insights into receptor assembly.The Journal of biological chemistry · 2022Article
- The Ins and Outs of Antigen Uptake in B cells.Frontiers in immunology · 2022Review
- Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses.EMBO reports · 2021Article
- Article
- Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The role of actin and myosin in antigen extraction by B lymphocytes.Seminars in cell & developmental biology · 2020Review
- Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data.OncoTargets and therapy · 2020Review
- Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Pathogenic B-cell receptor signaling in lymphoid malignancies: New insights to improve treatment.Immunological reviews · 2019Review
- The immunobiology of ubiquitin-dependent B cell receptor functions.Molecular immunology · 2018Review
- Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK.Antibodies (Basel, Switzerland) · 2017Article
- Mechanisms of central tolerance for B cells.Nature reviews. Immunology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system.
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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.