The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4+ T‐cell Responses to MBP in Health and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune condition characterized by degeneration of nerve fibre myelin sheets. A candidate autoantigen, myelin basic protein (MBP), has especially attracted attention. The presence of anti‐MBP antibodies is a predictor of definite MS, but their role in the pathogenesis remains obscure. T cells have long been known to play a pivotal role in the pathogenesis of MS. Recently, an important role for B cells as autoantigen‐presenting cells has been demonstrated in other autoimmune diseases, including rheumatoid arthritis and diabetes. The uptake of MBP by B cells and the presentation of MBP‐derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease‐associated anti‐MBP antibodies in MS patients, respectively. We have investigated the formation of MBP‐containing IC, the binding of MBP to B cells, the MBP‐elicited induction of Th‐cell and B‐cell proliferation and the cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors grown in the presence of intact or C‐inactivated serum from healthy donors or patients with MS. While MBP did not induce measurable proliferation of B cells nor CD4+ T cells, we observed the production of TNF‐α, IFN‐γ and IL‐10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. By contrast, no production of IL‐2, IL‐4 and IL‐5 was detected. We are currently investigating the capability of MS sera to promote the formation of MBP‐containing IC and thereby enhance the cytokine responses, by virtue of elevated anti‐MBP contents.