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CD40, also known as TNFSF5, is a type I transmembrane protein and member of the TNF receptor family. The binding of CD40L (CD154) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects (1). CD40 is expressed on B cells, dendritic cells, monocytes, thymic epithelial cells and, at low levels, on T cells (2). Signaling though CD40 plays an important role in the proliferation and differentiation of B cells and is critical for immunoglobulin (Ig) class switching (3). The membrane-anchored CD40L is expressed almost exclusively on activated CD4+ T lymphocytes. Failure to express CD40L leads to "immunodeficiency with hyper-IgM", a disease characterized by failure to produce IgG, IgA and IgE. Some of the early intracellular signaling by the CD4-CD40L system includes the association of the CD40 with TRAFs and the activation of various kinases (4). Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of CD4-CD40L is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis.