Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease.
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.
Wilkinson
Ray
R
Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Lyons
A Bruce
AB
Roberts
Donna
D
Wong
Mae-Xhum
MX
Bartley
Paul A
PA
Jackson
Denise E
DE
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000209:etiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001853:Bone Marrow / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000187:drug effects* / Q000502:physiology
D001323:Autoantibodies; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011947:Receptors, Antigen, B-Cell