Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, or CNS.1,2
Although the exact cause of MS is not clear1, the pathogenic process involves the lymph nodes where T and B cells interact, initially outside the CNS, and later probably also in follicles inside the CNS.1
B cells are critical for mounting healthy immune responses. They release cytokines to protect the body from infection, produce antibodies to capture and eliminate antigens, and present antigens to T cells.3 When T cells encounter B cells presenting antigen in the lymph node, T-cell differentiation and proliferation are triggered.4
In people with MS, B cells capture auto-antigens derived from neurons or their myelin sheaths and present peptides they generate from these auto-antigens to T cells within the lymph nodes, thereby promoting activation of pathogenic (encephalitogenic) T cells.4 In other words, B cells direct T cells to attack the body’s CNS tissue.3
Homing signals—much like a GPS—help these autoreactive B cells and T cells navigate to the CNS, where they drive inflammation that damages the brain and/or spinal cord by inducing de-myelination, axonal damage and impaired transmission of nerve impulses.4,5 B cells may also produce pathogenic antibodies that contribute to the development of MS.3
MS is often characterized by relapses, disability progression, lesions and grey and white matter damage.6
Every person’s MS journey is unique, but many diagnosed with relapsing-remitting MS advance to secondary progressive MS, or SPMS.7,8
Inflammation and neurodegeneration damage myelin and axons from the start, though compensatory repair mechanisms may mask the initial clinical signs of this damage, making it difficult to identify progression early.6,9-12
In relapsing-remitting MS, progression occurs alongside relapses,11 driven by peripheral inflammation and lymphocyte infiltration of the CNS.10,13
As MS progresses, central inflammation and neurodegeneration become more prominent; compensatory repair mechanisms become exhausted and irreversible gray and white matter damage occurs.6,11,14
- Bittner S, Ruck T, Wiendl H, Grauer OM, Meuth SG. Targeting B cells in relapsing-remitting multiple sclerosis: from pathophysiology to optimal clinical management. Ther Adv Neurol Disord. 2017;10(1):51-66.
- Haider L, Zrzavy T, Hametner S, et al. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain. Brain. 2016;139(Pt 3):807-815.
- Archelos JJ, Storch MK, Hartung HP. The role of B cells and autoantibodies in multiple sclerosis. Ann Neurol. 2000;47(6):694-706.
- Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010;162(1):1-11.
- Pender MP, Greer JM. Immunology of multiple sclerosis. Curr Allergy Asthma Rep. 2007;7(4):285-292.
- Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14(2):183-193.
- Ontaneda D, Thompson AJ, Fox RJ, Cohen JA. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet. 2017;389(10076):1357-1366.
- Larochelle C, Uphaus T, Prat A, Zipp F. Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology? Trends Neurosci. 2016;39(5):325-339.
- Cree BAC, Hollenbach JA, et al. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019;85(5):653-666.
- Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545-558.
- Pérez-Cerdá F, Sánchez-Gómez MV, Matute C. The link of inflammation and neurodegeneration in progressive multiple sclerosis. Mult SclerDemeylinating Disord. 2016;1(9).
- Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012;8(11):647-656.
- Bradl M, Lassmann H. Progressive multiple sclerosis. Semin Immunopathol. 2009;31(4):455-465.
- Lassmann H. Targets of therapy in progressive MS. Mult Scler. 2017;23(12):1593-1599.