CD40LG Gene

CD40LG (CD40 ligand) is a protein-coding gene located on chromosome Xq26.3. The CD40 ligand encoded by the CD40LG gene on the X chromosome is expressed on the surface of T cells (Zhou Y et al. 2009). The CD40 ligand stimulates T cell proliferation and cytokine production . Its cross-linking on T cells generates a costimulatory signal that increases the production of IL4 and IL10 in conjunction with TCR/CD3 ligation and CD28 costimulation. CD40LG induces NF-kappa-B activation and MAPK8 and PAK2 kinase activation in T cells. Furthermore, CD40LG induces tyrosine phosphorylation of isoform 3 of CD28, mediating proliferation of B cells in the absence of a co-stimulus and IgE production in the presence of IL4. The ligand is involved in the switching of immunoglobulin classes.

CD40 ligand acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which has cell type-dependent effects, such as B-cell activation, NF-kappa-B signaling, and anti-apoptotic signaling.

A defect in this gene results in an inability to undergo immunoglobulin class switching.

Diseases associated with CD40LG include:

• "CD40 ligand deficiency".

Note: CD40 ligand (CD40LG) is overexpressed on lupus T cells (Zhou Y et al 2009).

1. Allen RC et al (1993) CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science 259: 990-993.
2. Andre P et al (2002) CD40L stabilizes arterial thrombi by a beta(3) integrin-dependent mechanism. Nature Med. 8: 247-252.
3. Aruffo A et al (1993) The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell 72: 291-300.
4. Aschermann Z et al (2007) X-linked hyper-IgM syndrome associated with a rapid course of multifocal leukoencephalopathy. Arch. Neurol. 64: 273-276.
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6. Kraakman ME et al (1995) Identification of a CD40L gene mutation and genetic counselling in a family with immunodeficiency with hyperimmunoglobulinemia M. Clin Genet 48: 46-48.
7. van Zelm MC et al. (2014) Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation. J Allergy Clin. Immun 134: 135-144.
8. Zhou Y et al (2009) T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus. Clin Immunol 132:362-370.