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.
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).
In the macrophage, the primary signal for activation is IFN-γ from Th1 type CD4T 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.
The B cell can present antigens to helper T cells. If an activated T cell recognizes the peptide presented by the B cell, the CD40L on the T cell binds to the B cell's CD40 receptor, causing resting B cell activation. The T cell also produces IL-4, which directly influences B cells. As a result of these stimulations, the B cell can undergo division, antibodyisotype 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. Early evidence for these effects were that in CD40 or CD154 deficient mice, there is little class switching or germinal centre formation, and immune responses are severely inhibited.
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