ArticleNature communications2021
CTLA-4 expression by B-1a B cells is essential for immune tolerance.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
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- Limited Clinical Benefit of Immune Checkpoint Inhibition in Ovarian Cancer with Opportunities in Selected Subtypes.International journal of molecular sciences · 2026Review
- Conserved noncoding sequence-9 regulates NFATc1-mediated IL-10 expression in B cells to control inflammatory responses.Science advances · 2026Article
- Immune-related adverse events in hepatocellular carcinoma: organ-specific patterns and management approaches.Journal of liver cancer · 2026Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- PI3Kdelta-driven expansion of regulatory B cells impairs protective immune responses to Trypanosoma congolense parasite infection.PLoS pathogens · 2025Article
- Neuromuscular complications associated with cancer immunotherapy.Journal of the National Cancer Center · 2025Review
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- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Gene-regulatory programs that specify age-related differences during thymocyte development.Cell reports · 2025Article
- IRnet: Immunotherapy response prediction using pathway knowledge-informed graph neural network.Journal of advanced research · 2025Article
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- Immune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Engineering Nanoparticles to Modulate Extracellular Matrix and Immune Components of the Tumor Microenvironment in Cancer Immunotherapy.Biomaterials research · 2025Review
- Immune checkpoint-based biomarkers for therapeutic response in patients with multiple sclerosis.Frontiers in immunology · 2025Observational
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 3 countries.
Funding
Abstract
CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life. This impaired immune homeostasis results from B-1a cell dysfunction upon loss of CTLA-4. Therefore, CTLA-4-deficient B-1a cells up-regulate epigenetic and transcriptional activation programs and show increased self-replenishment. These activated cells further internalize surface IgM, differentiate into antigen-presenting cells and, when reconstituted in normal IgH-allotype congenic recipient mice, induce GCs and Tfh cells expressing a highly selected repertoire. These findings show that CTLA-4 regulation of B-1a cells is a crucial immune-regulatory mechanism.
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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.