The CD40 antigen and its ligand

J Banchereau, F Bazan, D Blanchard… - Annual review of …, 1994 - annualreviews.org
J Banchereau, F Bazan, D Blanchard, F Brič, JP Galizzi, C Van Kooten, YJ Liu, F Rousset…
Annual review of immunology, 1994annualreviews.org
CD40 is an integral membrane protein found on the surface of B lym phocytes, dendritic
cells, follicular dendritic cells, hematopoietic pro genitor cells, epithelial cells, and
carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor
necrosis factor receptor super family. The CD40 gene maps to human chromosome 20q 1 1-
2-q 13-2. CD40 binds to a ligand (CD40-L) which is an 35 kDa glycoprotein of 261 aa, a
member of the tumor necrosis factor superfamily. The CD40-L gene maps to human …
Abstract
CD40 is an integral membrane protein found on the surface of B lym phocytes, dendritic cells, follicular dendritic cells, hematopoietic pro genitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor super family. The CD40 gene maps to human chromosome 20q 1 1-2-q 13-2. CD40 binds to a ligand (CD40-L) which is an 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-lO results in very high immunoglobulin production with limited cell proliferation. IL-IO induces naive B cells to produce IgG3, IgGI, and IgAl, and further addition ofTGFfJ permits the secretion ofIgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers:(i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype,(ii) CD40 activated B cells can undergo isotype switching,(iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ
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