Project R-3253

Study of the antibody dependent and independent B cell functions in multiple sclerosis (Research)

B cells are clearly implicated in the pathogenesis of multiple sclerosis (MS). Most research on B cells has focused on (auto)antibody production, but recent success of B cell depletion in MS treatment has renewed interest in B cell antigen presentation capacity. However, the antigen targets of autoreactive B cells remain largely unknown and the role of B cells as antigen-presenting cells in MS has not been studied in detail. Previously, we isolated for the first time clonally expanded B cells from both cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients. Moreover, we showed reactivity of peripheral B cells towards intracellular autoantigens and an oligodendroglioma (HOG) cell line. This project aims to further elucidate antibody dependent and independent B cell functions in MS. We will determine the autoantigens of the isolated clonally expanded and autoreactive B cells by immunoprecipitation and proteomic techniques. The prevalence and pathologic relevance of antibodies directed to these autoantigens is studied. Further, the capacity of peripheral B cells from MS patients to activate autologous T cells by presentation of myelin and other autoantigens is examined. These experiments will provide better insights into the aetiology of MS, which is instrumental for identification of novel therapeutic targets.

01 October 2011 - 30 September 2015