ArticleJournal of immunology (Baltimore, Md. : 1950)2015
TLR7- and TLR9-responsive human B cells share phenotypic and genetic characteristics.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Common variable immunodeficiency-associated endotoxemia promotes early commitment to the T follicular lineage.The Journal of allergy and clinical immunology · 2019Trial
- TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes.EBioMedicine · 2019Trial
- Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response.International journal of molecular sciences · 2026Review
- Evaluation of Antibodies Induced by Melanoma Helper Peptide Vaccine and Their Modulation by Vaccine Adjuvants.Vaccines · 2026Article
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.NeuroImmune pharmacology and therapeutics · 2023Article
- Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library.International journal of molecular sciences · 2023Article
- A Study on MDA5 Signaling in Splenic B Cells from an Imiquimod-Induced Lupus Mouse Model with Proteomics.Cells · 2022Article
- Pattern recognition receptor ligand-induced differentiation of human transitional B cells.PloS one · 2022Article
- Article
- Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in systemic lupus erythematosus.Lupus science & medicine · 2021Article
- Single-Cell Transcriptomic Analyses Define Distinct Peripheral B Cell Subsets and Discrete Development Pathways.Frontiers in immunology · 2021Article
- Serum Free Immunoglobulins Light Chains: A Common Feature of Common Variable Immunodeficiency?Frontiers in immunology · 2020Article
- FcRn Overexpression Expands Diversity of the Humoral Immune Response in bFcRn Transgenic Mice.Frontiers in immunology · 2020Article
- TLR9-Activating CpG-B ODN but Not TLR7 Agonists Triggers Antibody Formation to Factor IX in Muscle Gene Transfer.Human gene therapy methods · 2019Article
- Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation.Seminars in immunopathology · 2019Review
- Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.Microbiome · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
B cells activated by nucleic acid-sensing TLR7 and TLR9 proliferate and secrete immune globulins. Memory B cells are presumably more responsive due to higher TLR expression levels, but selectivity and differential outcomes remain largely unknown. In this study, peripheral blood human B cells were stimulated by TLR7 or TLR9 ligands, with or without IFN-α, and compared with activators CD40L plus IL-21, to identify differentially responsive cell populations, defined phenotypically and by BCR characteristics. Whereas all activators induced differentiation and Ab secretion, TLR stimulation expanded IgM(+) memory and plasma cell lineage committed populations, and favored secretion of IgM, unlike CD40L/IL-21, which drove IgM and IgG more evenly. Patterns of proliferation similarly differed, with CD40L/IL-21 inducing proliferation of most memory and naive B cells, in contrast with TLRs that induced robust proliferation in a subset of these cells. On deep sequencing of the IgH locus, TLR-responsive B cells shared patterns of IgHV and IgHJ usage, clustering apart from CD40L/IL-21 and control conditions. TLR activators, but not CD40L/IL-21, similarly promoted increased sharing of CDR3 sequences. TLR-responsive B cells were characterized by more somatic hypermutation, shorter CDR3 segments, and less negative charges. TLR activation also induced long positively charged CDR3 segments, suggestive of autoreactive Abs. Testing this, we found culture supernatants from TLR-stimulated B cells to bind HEp-2 cells, whereas those from CD40L/IL-21-stimulated cells did not. Human B cells possess selective sensitivity to TLR stimulation, with distinctive phenotypic and genetic signatures.
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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.