The human CD154 (CD40-ligand) is a 39 kDa type II membrane glycoprotein predominantly expressed on CD4+ T cells, but also on a small proportion of CD8+ cells and NK cells. It is belonging to the tumor necrosis factor (TNF) family, while its counterreceptor on B cells, CD40, is a member of the TNF receptor/nerve growth factor (NGF) receptor family. Interactions between CD40 on B cells and its ligand on activated T cells results in B cell activation, proliferation, aggregation, and immunoglobulin isotype switching. A defect in the gene encoding CD154 is responsible for X-linked immunoglobulin deficiency with normal or elevated IgM (X-linked hyper IgM). These patients produce IgM but fail to produce downstream Ig isotypes, suggesting that interaction between CD40 on B cells and its ligand on activated T cells plays a critical role in Ig heavy chain switch recombination. The expression of CD154 on activated T cells is tightly regulated. B cells down-regulate the expression of functional CD154 in activated T cells through inhibition of CD154 mRNA expression and release of soluble CD40 that binds CD154.Synonyms: CD40 ligand, CD40-L, CD40LG, GP39, T-cell antigen Gp39, TNF-related activation protein, TNFSF5, TRAP, Tumor necrosis factor ligand superfamily member 5