References were found by searching PubMed, between Jan, 2006, and March, 2008, with the terms “B cells”, “rituximab”, “natalizumab”, and “multiple sclerosis”. Articles identified from searches of the authors' own files were also included. Only papers written in English were included, which were further selected on the basis of originality and importance to the topic of the Personal View.
Personal ViewB cells and multiple sclerosis
Introduction
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS that is characterised by persistent intrathecal synthesis of immunoglobulins—mainly oligoclonal IgG—and recruitment of activated T cells and macrophages into the CNS. The antigenic stimuli that initiate or perpetuate this abnormal immune reactivity are still a matter of intense research and debate. In the past few years, the concept of MS as an autoimmune disease that is mediated by myelin-reactive T cells has been challenged, and reassessment of the role of B cells in the pathogenesis of the disease is ongoing.1, 2 Three sets of new data—the characterisation of B-cell follicle-like structures in the brain meninges of patients with MS,3, 4, 5 which extends the earlier description of lymphoid tissue in MS lesions;6 the finding that a substantial proportion of the B cells or plasma cells that accumulate in these follicles and in white-matter lesions are infected with Epstein-Barr virus (EBV);7 and the results of a trial with the B-cell-depleting antibody rituximab8—now provide reciprocal conceptual support for the prominent role of B cells in the pathogenesis of MS and disclose a possible scenario that links abnormal B-cell activation to T-cell-mediated immunopathology.
Section snippets
Triggers of B-cell activation
Traditionally, B cells have been implicated in MS through their ability to produce pathogenic antibodies or autoantibodies, which can destroy tissue by recruiting macrophages that express the Fc receptor and by activation of the complement pathway. The results of histopathological analyses indicate that antibodies might have an important role in plaque initiation9 and in demyelination in patients with established MS.10 The list of candidate pathogenic antigens in MS has recently grown longer;
Where next and conclusions
After years of impasse, new data on B cells are stimulating unconventional ways of reasoning about MS pathogenesis. The identification of antibodies to neuronal antigens provides clues about the mechanisms that underlie damage to brain tissue and deserve further investigation. The identification of ectopic B-cell follicles as a niche for the generation of B cells and plasma cells in the brain of patients with MS reinforces the concept that humoral immunity has a role in the pathological changes
Search strategy and selection criteria
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