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CD40LG gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

CD40LG gene

The CD40LG gene provides instructions for making CD40 ligand, a protein critical for immune system function and the maturation of antibody-producing B cells.

Normal Function

The CD40LG gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches to its receptor protein, CD40, located on the surface of B cells.

B cells are involved in the production of antibodies (immunoglobulins) that protect the body against infection. While B cells can mature to produce immunoglobulin M (IgM) independently, they require interaction between the CD40 receptor and CD40 ligand to mature into cells that produce other classes of antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). CD40 ligand is also necessary for T cell differentiation and interaction with other immune system cells.

Health Conditions Related to Genetic Changes

X-linked hyper IgM syndrome

More than 150 mutations in the CD40LG gene have been found to cause X-linked hyper IgM syndrome. These mutations lead to the production of an abnormal CD40 ligand or prevent its production entirely.

If CD40 ligand cannot attach to its receptor on B cells, these cells cannot produce IgG, IgA, or IgE antibodies. Furthermore, these mutations impair the T cell's ability to differentiate and interact with other immune cells. Consequently, people with this condition are more susceptible to infections due to a compromised immune system.

Other Names for This Gene

  • CD154
  • CD40 antigen ligand
  • CD40L
  • CD40L_HUMAN
  • gp39
  • hCD40L
  • HIGM1
  • IGM
  • IMD3
  • T-B cell-activating molecule
  • T-BAM
  • TNF-related activation protein
  • TNFSF5
  • TRAP
  • tumor necrosis factor (ligand) superfamily member 5

Frequently Asked Questions

Diagnosis typically begins with a complete blood count and immunoglobulin levels showing elevated or normal IgM but significantly low IgG, IgA, and IgE. To confirm the genetic cause, clinicians perform flow cytometry to measure the expression of CD40 ligand on activated T cells; a lack of surface CD40L is highly indicative. Definitive diagnosis is achieved through genetic testing that identifies specific mutations in the CD40LG gene on the X chromosome. This testing is crucial for distinguishing it from other forms of hyper IgM syndrome that may have different inheritance patterns and treatment responses.
X-linked hyper IgM syndrome primarily affects males because they have only one X chromosome; if it carries the mutation, they will develop the condition. Females have two X chromosomes, so they are usually carriers and are asymptomatic because the normal copy of the gene on their second X chromosome is sufficient for immune function. However, in rare cases of skewed X-inactivation, where the X chromosome with the mutation is preferentially active, female carriers may present with mild immune deficiencies or elevated IgM levels, though they rarely develop the full clinical picture seen in affected males.
Patients are particularly vulnerable to opportunistic infections, including Pneumocystis jirovecii pneumonia (PCP), Cryptosporidium (which can cause chronic diarrhea and biliary strictures), and severe bacterial infections of the lungs and sinuses. This susceptibility arises because the lack of IgG and IgA antibodies impairs the body's ability to neutralize pathogens and clear them from mucosal surfaces. Additionally, the defect in T cell function compromises the immune system's ability to coordinate a defense against intracellular organisms and fungi.
In a healthy immune system, B cells start by producing IgM antibodies. To switch to producing more effective antibodies like IgG, IgA, and IgE, B cells require a signal from T cells via the CD40 ligand. In X-linked hyper IgM syndrome, the CD40LG gene mutation prevents T cells from producing functional CD40 ligand. Without this signal, B cells cannot undergo class switching and remain stuck in the IgM production phase. Consequently, the body produces large amounts of IgM but fails to generate the other antibody classes needed for long-term immunity and mucosal protection.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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