CD40

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

Activated CD4+ T cells primarily exhibit its ligand CD40L/CD154 to antigen-presenting cells including dendritic cells (DCs), B cells, macrophages, classical and non-classical monocytes, on a variety of non-immune cells including platelets and endothelial cells, and on several types of tumor cells.

Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency.

Discovery

Between the late 1950s and the mid-1980s, several immunology laboratories started to use the new hybridoma technology to develop monoclonal antibodies (mAbs) and define receptors expressed at different stages of hematopoietic cell differentiation. The goal of these experiments was to identify differentiation antigens that could be used to describe the stages of lymphocyte differentiation and various functional cell subsets. While doing these experiments, several mAbs were developed against a protein called CD40, a surface receptor of B cells that can be polyclonally activated by a binding ligand. Over time, many features and purposes of the CD40 signaling pathway were discovered, including the discovery of CD40 ligand (CD154/CD40L), a T cell surface molecule which is capable of induction of contact dependent differentiation of B cells.

Function

The protein receptor encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation.