CD40, also known as TNFRSF5, Bp50, CDW40, MGC9013, or p50, is a member of the tumor necrosis factor (TNF) receptor superfamily. This family consists of single transmembrane-spanning glycoproteins that play crucial roles in mediating a broad range of immune and inflammatory responses. CD40 is particularly important for T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation.
CD40 features four cysteine-rich repeats in its extracellular domain and is expressed in B cells, dendritic cells, macrophages, endothelial cells, and several tumor cell lines. The extracellular domain of CD40 contains cysteine-rich repeat regions, which are characteristic of many receptors within the TNF superfamily.
The interaction of CD40 with its ligand, CD40L, leads to the aggregation of CD40 molecules. These aggregated molecules then interact with cytoplasmic components to initiate signaling pathways. Early studies on the CD40-CD40L system highlighted its role in humoral immunity. Defects in the CD40 pathway can result in hyper-IgM immunodeficiency type 3 (HIGM3), an autosomal recessive disorder. This condition is characterized by an inability of B cells to undergo isotype switching and to mount an antibody-specific immune response, as well as a lack of germinal center formation.