CD40/4-1BBL Antibodies

Target Information

CD40 is a single-chain glycoprotein and a member of the tumor necrosis factor receptor (TNFR) family, exhibiting significant homology to the Hodgkin's disease-associated antigen, CD30. It is expressed by B lymphocytes, follicular dendritic cells, thymic epithelium, and a subset of peripheral T cells, as well as some epithelial cells, carcinomas, and lymphoid dendritic cells. Notably, CD40 is present on all B cells except plasma cells. CD40 plays a crucial role in regulating B cell development and maturation, inducing immunoglobulin isotype-switching, and protecting B cells from surface Ig-induced apoptosis when combined with other signals such as IL-4. It promotes proliferation and is essential for T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. The interaction between CD40 and its ligand CD154 (gp39) on T cells is vital for T-B cell crosstalk, costimulation, and immune regulation. Adaptor protein TNFR2 interacts with CD40, mediating signal transduction, while the AT-hook transcription factor AKNA is reported to regulate CD40 expression, which may be important for homotypic cell interactions. Additionally, the interaction between CD40 and its ligand is necessary for amyloid-beta-induced microglial activation, suggesting a role in the early pathogenesis of Alzheimer's disease. Two alternatively spliced transcript variants encoding distinct isoforms of CD40 have been identified. Diseases associated with CD40 dysfunction include Type 3 Hyper-IgM immunodeficiency and CD40 ligand deficiency, highlighting its importance in immune and inflammatory responses.

CD137 ligand (CD137L) is a type II membrane protein and part of the TNF superfamily. CD137L is a co-stimulatory molecule that is expressed on antigen presenting cells (DCs, monocytes/macrophages, B cells) and is upregulated upon activation. Its receptor, CD137/4-1BB, is found on a variety of cells, including inflamed endothelial cells, where its expression enhances extravasation of CD137L expressing monocytes. Activated T cells also express CD137, and engagement with CD137L enhances T cell proliferation, IL-2 secretion, survival, and cytotoxic activity. CD137L is also expressed on a majority of B-cell lymphomas, including mantle cell lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (but it is lacking on Hodgkin lymphoma and T-cell lymphoma). CD137L is also expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interactions.