ArticleThe Journal of experimental medicine2020
Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- SorLA regulates B cell receptor uptake, trafficking, and B cell-mediated immune responses in vivo.The Journal of experimental medicine · 2026Article
- The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities.Blood cancer discovery · 2026Review
- Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation.The Journal of experimental medicine · 2024Article
- B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1.Frontiers in immunology · 2024Article
- Immune dysregulation caused by homozygous mutations in CBLB.The Journal of clinical investigation · 2022Article
- Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression.Oncogene · 2022Article
- The Ins and Outs of Antigen Uptake in B cells.Frontiers in immunology · 2022Review
- Role of B cells as antigen presenting cells.Frontiers in immunology · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even low-affinity BCRs efficiently capture and present sufficient antigen to T cells, whereas the latter do so more efficiently after acquiring high-affinity BCRs. We show here that antigen uptake and processing by naive but not GC B cells depend on Cbl and Cbl-b (Cbls), which consequently control naive B and cognate T follicular helper (Tfh) cell interaction and initiation of the GC reaction. Cbls mediate CD79A and CD79B ubiquitination, which is required for BCR-mediated antigen endocytosis and postendocytic sorting to lysosomes, respectively. Blockade of CD79A or CD79B ubiquitination or Cbls ligase activity is sufficient to impede BCR-mediated antigen processing and GC development. Thus, Cbls act at the entry checkpoint of the GC reaction by promoting naive B cell antigen presentation. This regulation may facilitate recruitment of naive B cells with a low-affinity BCR into GCs to initiate the process of affinity maturation.
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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 Socratic graph.