Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

TLR9 activation is defective in common variable immune deficiency.

Charlotte Cunningham-Rundles1, Lin Radigan, Adina K Knight

  • 1Department of Medicine and the Immunobiology Center, Mount Sinai Medical Center, New York, NY 10029, USA. Charlotte.Cunningham-Rundles@MSSM.edu

Journal of Immunology (Baltimore, Md. : 1950)
|January 21, 2006
PubMed
Summary

Common variable immune deficiency (CVID) involves impaired B cell responses due to Toll-like receptor 9 (TLR9) defects. These defects hinder innate immune activation by CpG-DNA, affecting B cell function and plasmacytoid dendritic cell responses.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.

The Journal of experimental medicine·2026
Same author

Gastric Cancer Treated with 5-Fluorouracil following Discontinuation of Adjuvant S1 plus Docetaxel and Capecitabine plus Oxaliplatin due to Drug-Induced Acute Pancreatitis: A Case Report.

Case reports in oncology·2026
Same author

Hepatic Steatosis Detected by Abdominal Ultrasonography Is Associated With Worse Prognosis in Underweight Patients.

Hepatology research : the official journal of the Japan Society of Hepatology·2026
Same author

Letter to the Editor: "Quantifying the Delivered Dose of Bulevirtide in Clinical Trials and Real-World Use: A Dose Recovery Study".

Journal of hepatology·2026
Same author

A novel robot for CT-guided bone needle insertion with a rotational drilling and force-feedback speed control mechanism: preliminary evaluation in swine.

Japanese journal of radiology·2026
Same author

Insights into Clinical Challenges and Management of Primary and Secondary Antibody Deficiency in Pregnancy.

The journal of allergy and clinical immunology. In practice·2026

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Common variable immune deficiency (CVID) is a primary immune disorder marked by low immunoglobulin levels and impaired B cell function.
  • Genetic underpinnings for most CVID cases remain elusive, despite known defects in T, B, and dendritic cells.

Purpose of the Study:

  • To investigate the role of Toll-like receptor 9 (TLR9) in B cell and plasmacytoid dendritic cell activation in CVID patients.
  • To identify potential molecular defects in TLR9 signaling pathways contributing to CVID pathogenesis.

Main Methods:

  • Analysis of B cell and plasmacytoid dendritic cell activation in response to CpG-DNA, a TLR9 ligand.
  • Assessment of cell surface marker expression (e.g., CD86), cytokine production (IL-6, IL-10, IFN-alpha), and TLR9 expression (protein and mRNA) in CVID and healthy controls.

Related Experiment Videos

  • Sequencing of TLR9 gene to identify mutations or polymorphisms.

    • Main Results:

    • CVID B cells exhibited defective upregulation of CD86 and impaired production of IL-6 and IL-10 upon CpG-DNA stimulation.
    • Reduced expression of TLR9 protein and mRNA was observed in CVID B cells.
    • CpG-DNA-activated CVID plasmacytoid dendritic cells produced lower levels of IFN-alpha, despite normal intracellular TLR9 levels.
    • No mutations or polymorphisms in the TLR9 gene were identified in CVID patients.

    Conclusions:

    • Broad defects in TLR9 activation pathways are present in CVID, impacting both B cells and plasmacytoid dendritic cells.
    • These TLR9 defects likely contribute to impaired innate immune responses initiated by CpG-DNA, leading to compromised B cell function and potentially altered dendritic cell activity in CVID.
    • The identified TLR9 activation defects offer potential therapeutic targets for managing CVID, independent of specific genetic mutations.