Identification of auto-antigens in Myasthenia Gravis by using B cell immortalization

Abstract

Myasthenia Gravis (MG) is an autoimmune disorder in which auto-antibodies mainly bind to the acetylcholine receptor (AChR), present on the postsynaptic membrane of the neuromuscular junction (NMJ). The auto-antibodies cause an impaired neuromuscular transmission resulting in muscle weakness. Remarkably, thymic abnormalities such as hyperplasia, thymoma and germinal centre formation are often present in MG patients. Moreover, thymocytes from MG thymi have been shown to produce anti-AChR antibodies in vitro. Therefore, intrathymic auto-antibody production might explain why most MG patients benefit from thymectomy. However, a single B cell clone that produces auto-antibodies against AChR has not been identified yet. We hypothesize that Epstein-Barr Virus (EBV)-immortalized B cell clones from MG thymi will produce monoclonal auto-antibodies against the AChR.