Unraveling B lymphocytes in CNS inflammatory diseases Distinct mechanisms and treatment targets
- 20 October 2020
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 95 (16), 733-744
- https://doi.org/10.1212/WNL.0000000000010789
Abstract
Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic mechanisms of B lymphocytes in CNS inflammatory diseases. It has been demonstrated that B lymphocytes participate in the pathogenesis of these conditions as antigen-presenting cells, producing proinflammatory cytokines that induce Th1 and Th17 responses and producing antibodies. However, they are also able to produce anti-inflammatory cytokines, such as interleukin-10, functioning as regulators of autoimmunity. Understanding these diverse effects is essential for the development of focused treatments. In this review, we discuss the possible mechanisms that underlie B-lymphocyte involvement in MS, NMOSD, and AE and the outcomes obtained by treatments targeting B lymphocytes.This publication has 58 references indexed in Scilit:
- Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosisMultiple Sclerosis Journal, 2012
- Therapeutic plasma exchange for the treatment of anti‐NMDA receptor encephalitisJournal of Clinical Apheresis, 2011
- Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximabNeurology, 2011
- Cutting Edge: Novel Function of B Cell-Activating Factor in the Induction of IL-10–Producing Regulatory B CellsThe Journal of Immunology, 2010
- Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in miceBrain, 2010
- Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratomaActa Neuropathologica, 2009
- The Immunopathology of Multiple Sclerosis: An OverviewBrain Pathology, 2007
- The role of APRIL and BAFF in lymphocyte activationCurrent Opinion in Immunology, 2005
- Receptor editing is the main mechanism of B cell tolerance toward membrane antigensNature Immunology, 2004
- B cells regulate autoimmunity by provision of IL-10Nature Immunology, 2002