Antibody formation and immunomodulation in experimental allergic encephalomyelitis and multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease characterized by perivascular accumulation of infiammatory cells, resulting in numerous (multiple) plaques (sclerosis), in the central nervous system (CNS). Despite ample research efforts both etiology and pathogenicity of the disease remain largely unknown. Due to the complexity of clinical manifestations the unequivocal diagnosis of MS is difficult to make. It is generally accepted that the effector phase of the disease depends on an autoimmune reaction. Notwithstanding the fact that oligoclonal antibodies can be found in the cerebrospinal fluid during disease, the role of antibodies in MS is still unclear. In order to investigate the involvement of autoantigen specific antibodies in the pathology of MS, we performed a study to detect antigen specific B-cells (AFCs) in CNS tissues of MS patients. Using a new immunohistochemical technique we have revealed that a significant part of the AFCs localized in MS brain is specific for myelin basic protein (MBP). This provides further evidence for the local involvement of anti-MBP antibodies in the pathogenesis of MS. Production of antibodies by B-cells is critically dependent on T-cell help. It has been shown that interactions between the gp39 T-cell marker and its CD40 ligand on B-cells are essential for B-cell activation. In our experiments we have revealed gp39 positive T-cells in the same affected eNS tissue areas (plaques) in which we have detected the MBP specific AFe. The presence of both gp39t Th-cells and MBP specific B-cells in plaques of MS patients CNS tissues indicates that autoantigen specific B-cells can be activated directly within the CNS.

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