ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Functional Differences between IgM and IgD Signaling in Chronic Lymphocytic Leukemia.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- The cytoskeletal control of B cell receptor and integrin signaling in normal B cells and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro.Cell reports methods · 2025Article
- Article
- The malignant transformation potential of the oncogene STYK1/NOK at early lymphocyte development in transgenic mice.Biochemistry and biophysics reports · 2024Article
- Targeted small molecule therapy and inhibitors for lymphoma.Future medicinal chemistry · 2024Review
- Chronic Lymphocytic Leukemia: Disease Biology.Acta haematologica · 2024Review
- Mice Overexpressing Wild-TypeCancers · 2023Article
- Hyper-IgD Syndrome: Caused by Deficiency on Ras Prenylation and Trained Immunity?Journal of clinical immunology · 2023Article
- Article
- 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
- Review
- B cell receptor isotypes differentially associate with cell signaling, kinetics, and outcome in chronic lymphocytic leukemia.The Journal of clinical investigation · 2022Article
- Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism.Leukemia · 2021Article
- Primary Immune Responses and Affinity Maturation Are Controlled by IgD.Frontiers in immunology · 2021Article
- DAPK3 participates in the mRNA processing of immediate early genes in chronic lymphocytic leukaemia.Molecular oncology · 2020Article
- Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines.Scientific reports · 2020Article
- The importance of B cell receptor isotypes and stereotypes in chronic lymphocytic leukemia.Leukemia · 2019Review
- Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies.JCI insight · 2018Article
- Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy.Nature reviews. Clinical oncology · 2018Review
- Targeting B cell receptor signalling in cancer: preclinical and clinical advances.Nature reviews. Cancer · 2018Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
BCR signaling is a central pathogenetic pathway in chronic lymphocytic leukemia (CLL). Most CLL cells express BCRs of IgM and IgD isotypes, but the contribution of these isotypes to functional responses remains incompletely defined. We therefore investigated differences between IgM and IgD signaling in freshly isolated peripheral blood CLL cells and in CLL cells cultured with nurselike cells, a model that mimics the lymph node microenvironment. IgM signaling induced prolonged activation of ERK kinases and promoted CLL cell survival, CCL3 and CCL4 chemokine secretion, and downregulation of BCL6, the transcriptional repressor of CCL3 In contrast, IgD signaling induced activation of the cytoskeletal protein HS1, along with F-actin polymerization, which resulted in rapid receptor internalization and failure to support downstream responses, including CLL cell survival and chemokine secretion. IgM and IgD receptor downmodulation, HS1 and ERK activation, chemokine secretion, and BCL6 downregulation were also observed when CLL cells were cocultured with nurselike cells. The Bruton's tyrosine kinase inhibitor ibrutinib effectively inhibited both IgM and IgD isotype signaling. In conclusion, through a variety of functional readouts, we demonstrate very distinct outcomes of IgM and IgD isotype activation in CLL cells, providing novel insight into the regulation of BCR signaling in CLL.
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Registered trials
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