Regulation of B cell activation by PECAM-1: implications for the development of autoimmune disorders.
Regulation of B-cell development and activation is imperative to the myriad of activities that perpetuate humoral immunity. This T-cell dependent immune mechanism often relies upon the maintenance of T-cell tolerance, such that the maturity of the antigen-presentating cell, its function and molecular mimicry are contributing factors. Recent findings have implicated the involvement of the B-cell and their corresponding surface co-receptors in regulating autoimmune disease. One candidate receptor, PECAM-1, has demonstrated the ability to downregulate both B and T-cell signalling pathways. The deletion of PECAM-1 in mice has led to a hyper-responsive B-cell phenotype with abnormal B-cell development. Additionally, in vivo functional studies have found that absence of PECAM-1 results in an increased susceptibility to autoimmune disorders of encephalomyelitis and Type I hypersensitivity reactions. Taken together, these findings indicate that PECAM-1 may have an important role in maintaining B-cell tolerance and regulatory function in preventing the onset of autoimmune disease. Elucidating the mechanisms of PECAM-1 function in autoimmune disorders could facilitate development of novel therapeutics.
Wong
Mae-Xhum
MX
Kronheimer Building, Austin Research Institute, A & RMC, Studley Road, Heidelberg, Victoria, Australia.
Jackson
Denise E
DE
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1