CD154

CD154, also called CD40 ligand or CD40L, is a is_associated_with::protein that is primarily expressed on activated is_associated_with::T cells and is a member of the TNF superfamily of molecules. It binds to is_associated_with::CD40 on is_associated_with::antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In total CD40L has three binding partners: CD40, α5β1 integrin and αIIbβ3. CD154 acts as a costimulatory molecule and is particularly important on a subset of is_associated_with::T cells called T follicular helper cells (TFH cells). On TFH cells, CD154 promotes is_associated_with::B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo is_associated_with::immunoglobulin class switching and is associated with is_associated_with::hyper IgM syndrome. Absence of CD154 also stops the formation of is_associated_with::germinal centers and therefore prohibiting antibody is_associated_with::affinity maturation, an important process in the is_associated_with::adaptive immune system.

Expression
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).

Macrophages
In the is_associated_with::macrophage, the primary signal for activation is IFN-γ from Th1 type is_associated_with::CD4 is_associated_with::T cells. The secondary signal is CD40L on the T cell, which binds is_associated_with::CD40 on the is_associated_with::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
is_associated_with::B cells can present is_associated_with::antigens to a specialized group of is_associated_with::helper T cells called TFH cells. If an activated TFH cell recognizes the peptide presented by the B cell, the CD40L on the T cell binds to the B cell's CD40, causing B cell activation. The T cell also produces IL-4, which directly influences B cells. As a result of this stimulation, the B cell can undergo rapid cellular division to form a is_associated_with::germinal center where is_associated_with::antibody is_associated_with::isotype switching and is_associated_with::affinity maturation occurs, as well as their differentiation to is_associated_with::plasma cells and is_associated_with::memory B 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 is_associated_with::class switching or is_associated_with::germinal centre formation, and immune responses are severely inhibited.

Endothelial cells
Activation of is_associated_with::endothelial cells by CD40L (e.g. from activated is_associated_with::platelets) leads to is_associated_with::reactive oxygen species production, as well as is_associated_with::chemokine and is_associated_with::cytokine production, and expression of adhesion molecules such as is_associated_with::E-selectin, is_associated_with::ICAM-1, and is_associated_with::VCAM-1. This inflammatory reaction in endothelial cells promotes recruitment of leukocytes to lesions and may potentially promote atherogenesis. CD40L has shown to be a potential biomarker for atherosclerotic instability.

Interactions
CD154 has been shown to interact with is_associated_with::RNF128.