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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.
Glossary
- ADCC=
- antibody-dependent cellular cytotoxicity;
- AE=
- autoimmune encephalitis;
- APC=
- antigen-presenting cell;
- APRIL=
- a proliferation-inducing ligand;
- AQP4=
- anti–aquaporin-4;
- ARR=
- annualized relapse rate;
- BAFF=
- B cell–activating factor;
- BBB=
- blood-brain-barrier;
- BCR=
- B-cell receptor;
- B-regs=
- regulatory B lymphocytes;
- CDCC=
- complement-dependent cytotoxicity;
- COVID-19=
- coronavirus disease 2019;
- EAE=
- experimental autoimmune encephalitis;
- IFN=
- interferon;
- Ig=
- immunoglobulin;
- IL=
- interleukin;
- IVIg=
- intravenous immunoglobulin;
- GM-CSF=
- granulocyte-macrophage colony-stimulating factor;
- anti-NMDAR=
- anti–NMDA receptor;
- NMOSD=
- neuromyelitis optica spectrum disorder;
- mAb=
- monoclonal antibody;
- MS=
- multiple sclerosis;
- OCB=
- oligoclonal band;
- PML=
- progressive multifocal leucoencephalopathy;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing-remitting MS;
- TLR=
- Toll-like receptor;
- TNF=
- tumor necrosis factor;
- Tregs=
- T regulatory cells
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received January 23, 2020.
- Accepted in final form August 3, 2020.
- © 2020 American Academy of Neurology
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