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.