The Role of B Cells in Multiple Sclerosis: Current and Future Therapies

Overview

Journal Cell Immunol

Publisher Elsevier

Specialties Allergy & Immunology
Cell Biology

Date 2019 May 28

PMID 31130183

Citations 17

Authors

Austin Negron

Rachel R Robinson

Olaf Stuve

Thomas G Forsthuber

Affiliations

Soon will be listed here.

Abstract

While it was long held that T cells were the primary mediators of multiple sclerosis (MS) pathogenesis, the beneficial effects observed in response to treatment with Rituximab (RTX), a monoclonal antibody (mAb) targeting CD20, shed light on a key contributor to MS that had been previously underappreciated: B cells. This has been reaffirmed by results from clinical trials testing the efficacy of subsequently developed B cell-depleting mAbs targeting CD20 as well as studies revisiting the effects of previous disease-modifying therapies (DMTs) on B cell subsets thought to modulate disease severity. In this review, we summarize current knowledge regarding the complex roles of B cells in MS pathogenesis and current and potential future B cell-directed therapies.

Citing Articles

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Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.

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Delgado S, Faissner S, Linker R, Rammohan K J Neurol. 2023; 271(4):1515-1535.

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References

Baranzini S, Jeong M, Butunoi C, MURRAY R, Bernard C, Oksenberg J . B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions. J Immunol. 1999; 163(9):5133-44. View

Lyons J, San M, Happ M, Cross A . B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide. Eur J Immunol. 1999; 29(11):3432-9. DOI: 10.1002/(SICI)1521-4141(199911)29:11<3432::AID-IMMU3432>3.0.CO;2-2. View

van der Goes A, Kortekaas M, Hoekstra K, Dijkstra C, Amor S . The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages. J Neuroimmunol. 1999; 101(1):61-7. DOI: 10.1016/s0165-5728(99)00133-2. View

Colombo M, Dono M, Gazzola P, Roncella S, Valetto A, Chiorazzi N . Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients. J Immunol. 2000; 164(5):2782-9. DOI: 10.4049/jimmunol.164.5.2782. View

Duda P, Schmied M, Cook S, Krieger J, Hafler D . Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest. 2000; 105(7):967-76. PMC: 377485. DOI: 10.1172/JCI8970. View

Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H . Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000; 47(6):707-17. DOI: 10.1002/1531-8249(200006)47:6<707::aid-ana3>3.0.co;2-q. View

Hennecke J, Wiley D . T cell receptor-MHC interactions up close. Cell. 2001; 104(1):1-4. DOI: 10.1016/s0092-8674(01)00185-4. View

Macpherson A, Lamarre A, McCoy K, Harriman G, Odermatt B, Dougan G . IgA production without mu or delta chain expression in developing B cells. Nat Immunol. 2001; 2(7):625-31. DOI: 10.1038/89775. View

McQualter J, Darwiche R, Ewing C, Onuki M, Kay T, Hamilton J . Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J Exp Med. 2001; 194(7):873-82. PMC: 2193476. DOI: 10.1084/jem.194.7.873. View

10.

Arnett H, Mason J, Marino M, Suzuki K, Matsushima G, Ting J . TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001; 4(11):1116-22. DOI: 10.1038/nn738. View

11.

Rivera A, Chen C, Ron N, Dougherty J, Ron Y . Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations. Int Immunol. 2001; 13(12):1583-93. DOI: 10.1093/intimm/13.12.1583. View

12.

Correale J, de Los Milagros Bassani Molinas M . Oligoclonal bands and antibody responses in multiple sclerosis. J Neurol. 2002; 249(4):375-89. DOI: 10.1007/s004150200026. View

13.

Mackay F, Browning J . BAFF: a fundamental survival factor for B cells. Nat Rev Immunol. 2002; 2(7):465-75. DOI: 10.1038/nri844. View

14.

Schlissel M . Allelic exclusion of immunoglobulin gene rearrangement and expression: why and how?. Semin Immunol. 2002; 14(3):207-212; discussion 225-6. DOI: 10.1016/s1044-5323(02)00044-1. View

15.

Fillatreau S, Sweenie C, McGeachy M, Gray D, Anderton S . B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002; 3(10):944-50. DOI: 10.1038/ni833. View

16.

Marusic S, Miyashiro J, Douhan 3rd J, Konz R, Xuan D, Pelker J . Local delivery of granulocyte macrophage colony-stimulating factor by retrovirally transduced antigen-specific T cells leads to severe, chronic experimental autoimmune encephalomyelitis in mice. Neurosci Lett. 2002; 332(3):185-9. DOI: 10.1016/s0304-3940(02)00947-3. View

17.

Alter A, Duddy M, Hebert S, Biernacki K, Prat A, Antel J . Determinants of human B cell migration across brain endothelial cells. J Immunol. 2003; 170(9):4497-505. DOI: 10.4049/jimmunol.170.9.4497. View

18.

Drayton D, Ying X, Lee J, Lesslauer W, Ruddle N . Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med. 2003; 197(9):1153-63. PMC: 2193975. DOI: 10.1084/jem.20021761. View

19.

Qin Y, Duquette P, Zhang Y, Olek M, Da R, Richardson J . Intrathecal B-cell clonal expansion, an early sign of humoral immunity, in the cerebrospinal fluid of patients with clinically isolated syndrome suggestive of multiple sclerosis. Lab Invest. 2003; 83(7):1081-8. DOI: 10.1097/01.lab.0000077008.24259.0d. View

20.

Wardemann H, Yurasov S, Schaefer A, Young J, Meffre E, Nussenzweig M . Predominant autoantibody production by early human B cell precursors. Science. 2003; 301(5638):1374-7. DOI: 10.1126/science.1086907. View