ArticleThe Journal of allergy and clinical immunology2017
Heterozygosity for transmembrane activator and calcium modulator ligand interactor A144E causes haploinsufficiency and pneumococcal susceptibility in mice.
Article in The Journal of allergy and clinical immunology, 2017. 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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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
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- TNFRSF13B in B cell responses to organ transplantation.Human immunology · 2023Article
- TNFRSF13B genotypes control immune-mediated pathology by regulating the functions of innate B cells.JCI insight · 2021Article
- TNFRSF13B polymorphisms counter microbial adaptation to enteric IgA.JCI insight · 2021Article
- Article
- The five dimensions of B cell tolerance.Immunological reviews · 2019Review
- Rare TACI Mutation in a 3-Year-Old Boy With CVID Phenotype.Frontiers in pediatrics · 2019Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe B-cell receptor transmembrane activator and calcium modulator ligand interactor (TACI) is important for T-independent antibody responses. One in 200 blood donors are heterozygous for the TACI A181E mutation.
objectiveWe sought to investigate the effect on B-cell function of TACI A181E heterozygosity in reportedly healthy subjects and of the corresponding TACI A144E mutation in mice.
methodsNuclear factor κB (NF-κB) activation was measured by using the luciferase assay in 293T cells cotransfected with wild-type and mutant TACI. TACI-driven proliferation, isotype switching, and antibody responses were measured in B cells from heterozygous TACI A144E knock-in mice. Mouse mortality was monitored after intranasal pneumococcal challenge.
resultsLevels of natural antibodies to the pneumococcal polysaccharide component phosphocholine were significantly lower in A181E-heterozygous than TACI-sufficient Swedish blood donors never immunized with pneumococcal antigens. Although overexpressed hTACI A181E and mTACI A144E acted as dominant-negative mutations in transfectants, homozygosity for A144E in mice resulted in absent TACI expression in B cells, indicating that the mutant protein is unstable when naturally expressed. A144E heterozygous mice, such as TACI
conclusionThese results suggest that TACI A181E heterozygosity results in TACI haploinsufficiency with increased susceptibility to pneumococcal infection. This has important implications for asymptomatic TACI A181E carriers.
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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.