Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis (original) (raw)

2001, Proceedings of the National Academy of Sciences

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS is typified by a highly clonally restricted antigen-driven antibody response that is confined largely to the central nervous system. The major antigenic targets of this response and the role of antibody in disease pathogenesis remain unclear. To help resolve these issues, we cloned the IgG repertoire directly from active plaque and periplaque regions in MS brain and from B cells recovered from the cerebrospinal fluid of a patient with MS with subacute disease. We found that high-affinity anti-DNA antibodies are a major component of the intrathecal IgG response in the patients with MS that we studied. Furthermore, we show DNA-specific monoclonal antibodies rescued from two subjects with MS as well as a DNA-specific antibody rescued from an individual suffering from systemic lupus erythematosus bound efficiently to the surface of neuronal cells and oligodendrocytes. For two of these antibodies, cell-surface recognition was DNA dependent. Our findings indicate that anti-DNA antibodies may promote important neuropathologic mechanisms in chronic inflammatory disorders, such as MS and systemic lupus erythematosus.

Contribution of Dysregulated B-Cells and IgE Antibody Responses to Multiple Sclerosis

Frontiers in Immunology

Multiple sclerosis (MS), a debilitating autoimmune inflammatory disease that affects the brain and spinal cord, causes demyelination of neurons, axonal damage, and neurodegeneration. MS and the murine experimental autoimmune encephalomyelitis (EAE) model have been viewed mainly as T-cell-mediated diseases. Emerging data have suggested the contribution of B-cells and autoantibodies to the disease progression. However, the underlying mechanisms by which dysregulated B-cells and antibody response promote MS and EAE remain largely unclear. Here, we provide an updated review of this specific subject by including B-cell biology and the role of B-cells in triggering autoimmune neuroinflammation with a focus on the regulation of antibody-producing B-cells. We will then discuss the role of a specific type of antibody, IgE, as it relates to the potential regulation of microglia and macrophage activation, autoimmunity and MS/EAE development. This knowledge can be utilized to develop new and ef...

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