Project R-3649

Characterization of B-cell functions in multiple sclerosis (Research)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which autoreactive B cells are clearly involved. Until now, research has mainly focused on the production of (auto)antibodies although the recent success of B cell depletion as a therapy for MS has increased interest in the antigen presentation function of B cells. However, the antigenic targets of autoreactive B cells remain largely unknown and the role of B cells as antigen presenting cells (APC) in MS has not been studied in detail. To further study the production of autoantibodies, we recently generated a large repertoire of immortalized B cell lines from peripheral blood and cerebrospinal fluid (CSF) of MS patients. Preliminary screening indicated several clonally expanded and human oligodendroglioma (HOG)-specific B cell clones. The aim of this project is to further characterize the autoreactive and clonally expanded B cell clones and to investigate the potential of B cells from MS patients to elicit autoreactive T cell responses. Reactivity of the generated B cell clones against myelin antigens, brain cell lines and viruses will be studied. Validation of their in vivo biological relevance will be investigated in EAE. The capacity of B cells to present autoantigens in MS will be examined by analyzing expression of costimulatory and MHC molecules together with B-T cell co-cultures. Results of this project could give more insight into the underlying disease processes and lead to novel therapeutic strategies.

01 January 2012 - 31 December 2014