Cluster of differentiation 40 ligand (CD40L (also known as CD154))

Cluster of differentiation 40 ligand (CD40L, also known as CD154) is a membrane glycoprotein primarily expressed on activated T lymphocytes. It belongs to the tumor necrosis factor superfamily and acts as a key costimulatory molecule by binding to its receptor, cluster of differentiation 40 (CD40), which is found mainly on antigen-presenting cells such as B cells, dendritic cells, macrophages, monocytes, endothelial cells, platelets, and some tumor types. The engagement between CD154/CD40L and CD40 triggers essential immune processes including immunoglobulin class switching in B lymphocytes—critical for effective antibody responses—memory B cell generation, germinal center formation within lymphoid tissues, cytokine production by both T-cells and monocytes/macrophages (e.g., IFN-gamma), proliferation signals within both arms of adaptive immunity (T/B-cells), anti-apoptotic signaling pathways via NF-kappa-B activation, and plays roles in inflammation-associated pathologies such as autoimmunity or cancer. Genetic defects affecting this protein cause X-linked hyper-IgM syndrome type 1—a primary immunodeficiency characterized by defective antibody maturation.

Other names

CD154TRAP (TNF-related activation protein)TNFSF5 (Tumor necrosis factor superfamily member 5)Gp39T-BAM (T-cell B-cell activating molecule)TBAMHIGM1IMD3

Drugs or antibodies targeting this molecule typically act by blocking the interaction between CD40 ligand on T cells and its receptor CD40 on antigen-presenting cells, thereby inhibiting downstream immune activation such as immunoglobulin class switching or inflammatory cytokine release.