Humoral immunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis

Abstract

Abnormal immunoglobulin synthesis within the central nervous system is a common finding in patients with multiple sclerosis (MS) that is often used for diagnosis. However, it is not clear whether antibodies, or the B-cells and plasma cells that make them, are critical to the pathogenesis of MS. Here we review the descriptive data that suggest a role for antibody in the pathogenesis of MS. The results of B-cell and antibody depletion studies in the animal model for MS, experimental autoimmune encephalomyelitis, are summarized, as well as early data using a chimeric monoclonal antibody to deplete B-cells in patients with MS.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

“…Synaptic plasticity in the spinal cord may explain, at least in part, the rapid sensorimotor recovery of the animals soon after tetraplegia (3,5). In view of the importance of a better understanding of MS as well as its experimental models, major advances in understanding how cellular and humoral immune responses contribute to the pathogenesis of these diseases have been made in recent years (8)(9)(10)(11)(12). Thus, targeting key elements of the immunological cascade that culminate in neural and glial tissue damage may offer a number of advantages over currently available treatment strategies (13)(14)(15)(16)(17).…”

Development of anti-CD20 therapy for multiple sclerosis

“…The emphasis on the role of T cells in MS pathogenesis and the controversy about role of B cells come from studies of the murine EAE model. EAE is induced by active immunization or passive transfer of myelin protein-specific CD4+ T cells but it is not induced by passive transfer of B cells or antibodies [10–11]. These findings led to initial acceptance of the paradigm that CD4+ T cells with Th1 polarization are the major pathogenic drivers of the disease.…”

“…While myelin basic protein has long been known to be an immunodominant antigen, myelin oligodendrocyte glycoprotein (MOG) can also ne specifically recognized by B-cells in MS patients. MOG is a minor Ag compared with other myelin proteins, but localized on the outer surface of the myelin sheets which makes it more accessible and induces strong B-cell response [10]. Antibodies to MOG induce EAE in non-human primates, augment MBP-induced EAE in Lewis rats and accelerate EAE in mice.…”

The role of B cells in multiple sclerosis: rationale for B-cell-targeted therapies

“…Although not specific for MS, intrathecal oligoclonal immunoglobulin is found in more than 90% of patients with definite MS [18]. IgG and IgM in the CSF can be identified by a pattern of oligoclonal bands when separated by electrophoresis.…”

“…MOG induces a strong B-cell response, probably because of its accessibility to antibodies on the outer lamellae of myelin and on the plasma membrane of myelinating oligodendrocytes [18,24]. Furthermore, MOG has been shown to elicit both B and T-cell-driven mechanisms in EAE [24].…”