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CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome)
PDB rendering based on 1aly.
Available structures
1aly, 1i9r
Identifiers
Symbols	CD40LG; TRAP; CD154; CD40L; HIGM1; IGM; IMD3; T-BAM; TNFSF5; gp39; hCD40L
External IDs	OMIM: 300386 MGI: 88337 HomoloGene: 56 GeneCards: CD40LG Gene
Gene ontology Molecular function • cytokine activity • tumor necrosis factor receptor binding • CD40 receptor binding Cellular component • extracellular space • soluble fraction • integral to plasma membrane • membrane Biological process • anti-apoptosis • inflammatory response • immune response • leukocyte adhesion • signal transduction • platelet activation • B cell proliferation • isotype switching • regulation of immunoglobulin secretion
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	959	21947
Ensembl	ENSG00000102245	ENSMUSG00000031132
UniProt	P29965	Q0VEI3
RefSeq (mRNA)	NM_000074	NM_011616
RefSeq (protein)	NP_000065	NP_035746
Location (UCSC)	Chr X: 135.56 - 135.57 Mb	Chr X: 53.56 - 53.57 Mb
PubMed search	[1]	[2]

CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In general, CD40L plays the role of a costimulatory molecule and induces activation in APC in association with T cell receptor stimulation by MHC molecules on the APC. In total CD40L has three binding partners: CD40, α5β1 integrin and αIIbβ3.

CD154 is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper IgM syndrome.^[1]

Expression of CD154

CD40 ligand is primarily expressed on activated CD4+ T lymphocytes but is also found in a soluble form. While CD40L was originally described on T lymphocytes, its expression has since been found on a wide variety of cells, including platelets, mast cells, macrophages, basophils, NK cells, B lymphocytes, as well as non-haematopoietic cells (smooth muscle cells, endothelial cells, and epithelial cells).^[2]

Specific effects on cells

Macrophages

In the macrophage, the primary signal for activation is IFN-γ from Th1 type CD4 T cells. The secondary signal is CD40L on the T cell, which binds CD40 on the macrophage cell surface. As a result, the macrophage expresses more CD40 and TNF receptors on its surface, which helps increase the level of activation. The activated macrophage can then destroy phagocytosed bacteria and produce more cytokines.

B cells

The B cell can present antigens to helper T cells. If the T cell recognizes the peptide presented by the B cell, the T cell synthesizes CD40L. The CD40L binds to the B cell's CD40 receptor, causing resting B cell activation. The T cell also produces IL-4, which directly binds to B cell receptors. As a result of this interaction, the B cell can undergo division, antibody isotype switching, and differentiation to plasma cells. The end-result is a B cell that is able to mass-produce specific antibodies against an antigenic target.

Endothelial cells

Activation of endothelial cells by CD40L (e.g. from activated platelets) leads to reactive oxygen species production, as well as chemokine and cytokine production, and expression of adhesion molecules such as E-selectin, ICAM-1, and VCAM-1. This inflammatory reaction in endothelial cells promotes recruitment of leukocytes to lesions and may potentially promote atherogenesis.^[3]

Interactions

CD154 has been shown to interact with RNF128.^[4]

References

Further reading

External links

• MeSH CD154+Antigen

PDB Gallery 1aly: CRYSTAL STRUCTURE OF HUMAN CD40 LIGAND   1i9r: STRUCTURE OF CD40L IN COMPLEX WITH THE FAB FRAGMENT OF HUMANIZED 5C8 ANTIBODY