Table 1.

Evidence supporting the role of B cells in the pathogenesis of multiple sclerosis

Biological data

Oligoclonal bands are present in the CSF of  > 90% of patients with MS throughout the disease stages [12, 32]  Brain-reactive B cells have been identified in the blood of some patients with MS [33, 34]; patients who display brain-reactive B cell responses both directly ex vivo and after polyclonal stimulation have a higher risk of subsequent relapses [33]  Gene expression data show that peripheral B cells are activated in the blood of patients in the early stage of acute optic neuritis, a common manifestation of MS [35]  B cell populations from some patients with MS include antigen autoreactive B cells that can stimulate T cell proliferation via antigen presentation [17, 36]  B cell epitope spreading contributes to disease development and progression in experimental autoimmune encephalomyelitis [37]

Pathological data

B cells persist in the inflamed CNS in MS and occupy distinct CNS compartments, including the CSF and white matter lesions, and among meningeal immune cell collections [12]  Immunoglobulin and activated complement components have been associated with demyelinating lesions in patients with MS [38]  Anti-myelin antibodies have been found within phagocytic cells in lesions of patients with MS [12]  B cell-rich lymphoid follicles have been found in the meninges of some patients (approximately 40–50%) with secondary-progressive MS [39, 40]

Clinical data

Anti-CD20 therapy has been shown to significantly reduce inflammatory lesions and clinical endpoints (relapses in patients with relapsing-remitting MS and clinical progression in those with primary-progressive MS) [41–44]  Other disease-modifying therapies with proven efficacy in relapsing-remitting MS have retrospectively been shown to have effects on B cells [14]

CNS central nervous system, CSF cerebrospinal fluid, MS multiple sclerosis