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Murine Model of CD40-activation of B cells
Published on: March 5, 2010
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A novel CD40LG mutation causing X‑linked hyper-IgM syndrome
Xuejing Li1, Yungai Cheng1, Dan Xu1
1Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Global Medical Genetics
|May 7, 2025
Summary
A novel mutation in the CD40 ligand gene (CD40LG) causes X-linked hyper-IgM (X-HIGM) by impairing T-B cell communication. This genetic defect leads to reduced memory B cells and altered T helper cell populations.
Area of Science:
- Immunology
- Genetics
Background:
- X-linked hyper-IgM (X-HIGM) is an immunodeficiency disorder resulting from CD40 ligand gene (CD40LG) mutations.
- It is characterized by impaired T-B lymphocyte interaction and defective class switch recombination (CSR).
Purpose of the Study:
- To investigate a Chinese family with X-HIGM.
- To identify a novel genetic defect in CD40LG and evaluate its impact on CD40L expression and lymphocyte subsets.
Main Methods:
- Flow cytometry was used to assess CD40L expression on activated CD4+ T cells and quantify lymphocyte subsets (including memory B cells and T helper cells).
- Genetic analysis identified mutations in the CD40LG gene.
Main Results:
- A novel CD40LG mutation (c.505_506del) was identified, leading to a frameshift (p.Y169Lfs*31) and a non-functional CD40L protein.
- Absence of CD40L expression on activated T cells was observed.
- Decreased memory B cells and a shift towards Th2 dominance with reduced Th1 and Th17 cells were noted.
Conclusions:
- The identified novel CD40LG mutation is pathogenic and causes X-HIGM.
- This finding expands the spectrum of CD40L variants associated with X-HIGM and deepens understanding of its molecular pathology.
