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Published on: October 31, 2016
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell
Ray Wilkinson1, A Bruce Lyons, Donna Roberts
1Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Abstract:
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is an immunoglobulin-immunoreceptor tyrosine-based inhibitory motif (Ig-ITIM) superfamily member that recruits and activates protein-tyrosine phosphatases, SHP-1 and SHP-2, through its intrinsic ITIMs. PECAM-1-deficient (PECAM-1(-/-) ) mice exhibit a hyperresponsive B-cell phenotype, increased numbers of B-1 cells, reduced B-2 cells, and develop autoantibodies. In the periphery, there are reduced mature recirculating B-2 cells and increased B-1a cells within the peritoneal cavity. In addition, PECAM-1(-/-) B cells display hyperproliferative responses to lipopolysaccharide and anti-IgM stimulation and showed enhanced kinetics in their intracellular Ca(++) response following IgM cross-linking. PECAM-1(-/-) mice showed increased serum levels of IgM with elevated IgG isotypes and IgA antidinitrophenol antibody in response to the T-independent antigen, dinitrophenol-Ficoll. Finally, PECAM-1(-/-) mice developed antinuclear antibodies and lupuslike autoimmune disease with age.
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