ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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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.
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Who cites it
66 citing papers in PubMed, 115 citations in OpenAlex.
- IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens.Blood · 2014Trial
- BAFF as a Key Modulator of Respiratory Mucosal B Cell Immunity in Viral Infection and Mucosal Vaccination.Cells · 2026Review
- Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells.Science advances · 2023Article
- Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice.Scientific reports · 2023Article
- Dysregulated MicroRNAs in the Pathogenesis of Systemic Lupus Erythematosus: A Comprehensive Review.International journal of biological sciences · 2023Review
- Review
- BAFF signaling drives interstitial transformation of mouse renal tubular epithelial cells in a Pin1-dependent manner.In vitro cellular & developmental biology. Animal · 2021Article
- Altered Systemic and Intestinal IgA Immune Responses in Individuals With Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2020Article
- Exposure to low temperatures suppresses the production of B-cell activating factor via TLR3 in BEAS-2B cells.Biochemistry and biophysics reports · 2020Article
- Gut microbial metabolites alter IgA immunity in type 1 diabetes.JCI insight · 2020Article
- Inflammation and tissue homeostasis: the NF-κB system in physiology and malignant progression.Molecular biology reports · 2020Review
- The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients.Scientific reports · 2020Article
- The regulators of BCR signaling during B cell activation.Blood science (Baltimore, Md.) · 2019Review
- CMV-Specific Immune Response-New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation.International journal of molecular sciences · 2019Article
- Deficient humoral responses and disrupted B-cell immunity are associated with fatal SFTSV infection.Nature communications · 2018Article
- Diversity of Immunoglobulin (Ig) Isotypes and the Role of Activation-Induced Cytidine Deaminase (AID) in Fish.Molecular biotechnology · 2018Review
- Interleukin-33 Contributes Toward Loss of Tolerance by Promoting B-Cell-Activating Factor of the Tumor-Necrosis-Factor Family (BAFF)-Dependent Autoantibody Production.Frontiers in immunology · 2018Article
- Article
- Intranasal immunization with a single dose of the fusion protein formulated with a combination adjuvant induces long-term protective immunity against respiratory syncytial virus.Human vaccines & immunotherapeutics · 2017Article
- The Role of BAFF System Molecules in Host Response to Pathogens.Clinical microbiology reviews · 2017Review
6 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
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Class switch DNA recombination (CSR) from IgM to IgG and IgA is crucial for antiviral immunity. Follicular B cells undergo CSR upon engagement of CD40 by CD40 ligand on CD4+ T cells. This T cell-dependent pathway requires 5-7 days, which is too much of a delay to block quickly replicating pathogens. To compensate for this limitation, extrafollicular B cells rapidly undergo CSR through a T cell-independent pathway that involves innate Ag receptors of the TLR family. We found that a subset of upper respiratory mucosa B cells expressed TLR3 and responded to viral dsRNA, a cognate TLR3 ligand. In the presence of dsRNA, mucosal B cells activated NF-kappaB, a transcription factor critical for CSR. Activation of NF-kappaB required TRIF (Toll/IL-1R domain-containing protein inducing IFN-beta), a canonical TLR3 adapter protein, and caused germline transcription of downstream CH genes as well as expression of AID (activation-induced cytidine deaminase), a DNA-editing enzyme essential for CSR. Subsequent IgG and IgA production was enhanced by BAFF (B cell-activating factor of the TNF family), an innate mediator released by TLR3-expressing mucosal dendritic cells. Indeed, these innate immune cells triggered IgG and IgA responses upon exposure to dsRNA. By showing active TLR3 signaling and ongoing CSR in upper respiratory mucosa B cells from patients with CD40 signaling defects, our findings indicate that viral dsRNA may initiate frontline IgG and IgA responses through an innate TLR3-dependent pathway involving BAFF.
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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.