ArticleNature communications2015
γ-Secretase directly sheds the survival receptor BCMA from plasma cells.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 238 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Belantamab Mafodotin, Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis
Who cites it
238 citing papers in PubMed, 4 syntheses or guidelines pooled it, 355 citations in OpenAlex.
- A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy.Anti-cancer agents in medicinal chemistry · 2025Pooled it
- Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma.Frontiers in immunology · 2024Pooled it
- Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.Frontiers in pharmacology · 2023Pooled it
- B-cell maturation antigen expression across hematologic cancers: a systematic literature review.Blood cancer journal · 2020Pooled it
- Similarities and differences of a proliferation-inducing ligand expression in lacrimal gland lesions of patients with IgG4-associated ophthalmic diseases and mucosa-associated lymphoid tissue lymphoma.Frontiers in immunology · 2025Trial
- Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- B cell-activating factor modulates the factor VIII immune response in hemophilia A.The Journal of clinical investigation · 2021Trial
- A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans.Frontiers in immunology · 2021Trial
- Soluble B-cell maturation antigen as a biomarker of progression and treatment response in patients with myeloma precursors.Blood neoplasia · 2026Article
- Imaging B cell maturation antigen in multiple myeloma.The Journal of clinical investigation · 2026Article
- Coexistent alterations of BAFF and B-cell phenotypes in complicated CVID course.The Journal of allergy and clinical immunology · 2026Article
- BAFF and APRIL Receptors in B Cell Immunity and Autoimmunity.Immunological reviews · 2026Review
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- BCMA-Engineered Dendritic Cell-Derived Exosomes as Bi-Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhanced BCMA Antigen Density Increases Trogocytosis and Attenuates CAR T cell Function.bioRxiv : the preprint server for biology · 2026Article
- Navigating the Therapeutic Landscape of Multiple Myeloma: Immunotherapy, Microenvironment, and Resistance.Biomedicines · 2026Review
- Structure and function of therapeutic antibodies approved by the US FDA in 2025.Antibody therapeutics · 2026Review
- Engineering Soluble Recombinant BCMA for Ide-Cel Labeling.European journal of immunology · 2026Article
178 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease. This direct shedding is facilitated by the short length of BCMA's extracellular domain. In vitro, γ-secretase reduces BCMA-mediated NF-κB activation. In addition, γ-secretase releases soluble BCMA (sBCMA) that acts as a decoy neutralizing APRIL. In vivo, inhibition of γ-secretase enhances BCMA surface expression in plasma cells and increases their number in the bone marrow. Furthermore, in multiple sclerosis, sBCMA levels in spinal fluid are elevated and associated with intracerebral IgG production; in systemic lupus erythematosus, sBCMA levels in serum are elevated and correlate with disease activity. Together, shedding of BCMA by γ-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.