CD40L plays a central role in costimulation and regulation of the immune response via
T cell priming and activation of CD40-expressing immune cells. At least 46 disease-causing mutations in this gene have been discovered.
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 (right), and several interaction molecules, the TH2-cell expressing CD40L.
B cells can present
antigens to a specialized group of
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
germinal center where
antibody isotype switching and
affinity maturation occurs, as well as their differentiation to
plasma cells and
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
class switching or
germinal centre formation, and immune responses are severely inhibited.
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. CD40L has shown to be a potential biomarker for atherosclerotic instability. == Interactions ==