mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2021.020mes-172Research ArticleОБЗОРREVIEWМеханизмы участия B-лимфоцитов в патогенезе рассеянного склерозаMechanisms of B lymphocyte involvement in the pathogenesis of multiple sclerosisМельниковМ. В.MelnikovM. V.

Михаил Валерьевич Мельников

ул. Островитянова, д. 1, г. Москва, 117997

Mikhail V. Melnikov

Ostrovitianova, 1, Moscow, 117997

medikms@yandex.ruРоговскийВ. С.RogovskiiV. S.

ул. Островитянова, д. 1, г. Москва, 117997

Ostrovitianova, 1, Moscow, 117997

ЛопатинаА. В.LopatinaA. V.

ул. Островитянова, д. 1, г. Москва, 117997

Ostrovitianova, 1, Moscow, 117997

СвиридоваА. А.SviridovaA. A.

ул. Островитянова, д. 1, г. Москва, 117997

Ostrovitianova, 1, Moscow, 117997

ВолковА. И.VolkovA. I.

ул. Островитянова, д. 1, г. Москва, 117997

Ostrovitianova, 1, Moscow, 117997

БойкоА. Н.BoykoA. N.

ул. Островитянова, д. 1, г. Москва, 117997

Ostrovitianova, 1, Moscow, 117997

Федеральный центр мозга и нейротехнологий Федерального медико-биологического агентства; Российский национальный исследовательский медицинский университет имени Н. И. Пирогова; Институт иммунологии Федерального медико-биологического агентстваРоссияFederal Center for Brain and Neurotechnology of Federal Medical-Biological Agency; Pirogov Russian National Research Medical University; Institute of Immunology of Federal Medical-Biological AgencyRussian FederationФедеральный центр мозга и нейротехнологий Федерального медико-биологического агентства; Российский национальный исследовательский медицинский университет имени Н. И. ПироговаРоссияFederal Center for Brain and Neurotechnology of Federal Medical-Biological Agency; Pirogov Russian National Research Medical University; Institute of Immunology of Federal Medical-Biological AgencyRussian FederationФедеральный центр мозга и нейротехнологий Федерального медико-биологического агентстваРоссияFederal Center for Brain and Neurotechnology of Federal Medical-Biological AgencyRussian Federation202127102024233106113Copyright © Мельников М.В., Роговский В.С., Лопатина А.В., Свиридова А.А., Волков А.И., Бойко А.Н., 20242024Мельников М.В., Роговский В.С., Лопатина А.В., Свиридова А.А., Волков А.И., Бойко А.Н.Melnikov M.V., Rogovskii V.S., Lopatina A.V., Sviridova A.A., Volkov A.I., Boyko A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/172

Рассеянный склероз (РС) — хроническое демиелинизирующее заболевание центральной нервной системы с аутоиммунным механизмом развития. Долгое время РС рассматривали как заболевание, опосредованное преимущественно Т-клетками. Однако исследования последних лет указывают на критическое патогенетическое значение B-лимфоцитов при РС. При РС B-клетки способны оказывать как про-, так и противовоспалительное действие. В статье рассмотрены основные механизмы участия B-клеток в патогенезе РС. Обсуждены диагностическая значимость оценки характеристик гуморального звена иммунной системы при демиелинизирующих заболеваниях, а также современные возможности модуляции функций B-клеток.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system involving autoimmune mechanisms. MS has been treated as a disorder mediated mainly by T cells for a long time. However, recent findings demonstrate that B lymphocytes are of crucial pathogenetic significance in MS. In patients with MS, B cells can possess both pro-inflammatory and anti-inflammatory effects. The paper reports the main mechanisms of B lymphocyte involvement in the pathogenesis of MS. Diagnostic value of assessing humoral immune parameters in individuals with demyelinating diseases and modern possibility of B cell function modulation are discussed.

B-клеткинейродегенерациянейровоспалениерассеянный склерозcellsneurodegenerationneuroinflammationmultiple sclerosisReferencesBoyko A, Melnikov M. Prevalence and incidence of multiple sclerosis in Russian Federation: 30 years of studies. Brain Sci. 2020 May 18; 10 (5): 305. DOI: 10.3390/brainsci10050305.Boyko A, Melnikov M. Prevalence and incidence of multiple sclerosis in Russian Federation: 30 years of studies. Brain Sci. 2020 May 18; 10 (5): 305. DOI: 10.3390/brainsci10050305.Kamali AN, Noorbakhsh SM, Hamedifar H, Jadidi-Niaragh F, Yazdani R, Bautista JM, et al. A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders. Mol Immunol. 2019 Jan; 105: 107–15. DOI: 10.1016/j.molimm.2018.11.015.Kamali AN, Noorbakhsh SM, Hamedifar H, Jadidi-Niaragh F, Yazdani R, Bautista JM, et al. A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders. Mol Immunol. 2019 Jan; 105: 107–15. DOI: 10.1016/j.molimm.2018.11.015.Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23; 16 (1): 272. DOI: 10.1186/s12974-019-1674-2.Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23; 16 (1): 272. DOI: 10.1186/s12974-019-1674-2.Milo R. Therapies for multiple sclerosis targeting B cells. Croat Med J. 2019 Apr 30; 60 (2): 87–98. DOI: 10.3325/cmj.2019.60.87.Milo R. Therapies for multiple sclerosis targeting B cells. Croat Med J. 2019 Apr 30; 60 (2): 87–98. DOI: 10.3325/cmj.2019.60.87.Corfe SA, Paige CJ. The many roles of IL7 in B cell development; mediator of survival, proliferation and differentiation. Semin Immunol. 2012; 24 (3), 198–208. DOI: 10.1016/j.smim.2012.02.001.Corfe SA, Paige CJ. The many roles of IL7 in B cell development; mediator of survival, proliferation and differentiation. Semin Immunol. 2012; 24 (3), 198–208. DOI: 10.1016/j.smim.2012.02.001.Bemark M. Translating transitions — how to decipher peripheral human B cell development. J Biomed Res. 2015; 29 (4): 264–84. DOI: 10.7555/JBR.29.20150035.Bemark M. Translating transitions — how to decipher peripheral human B cell development. J Biomed Res. 2015; 29 (4): 264–84. DOI: 10.7555/JBR.29.20150035.Kaminski DA, Wei C, Qian Y, Rosenberg AF, Sanz I. Advances in human B cell phenotypic profiling. Front Immunol 3. 2012; 302. DOI: 10.3389/fimmu.2012.00302.Kaminski DA, Wei C, Qian Y, Rosenberg AF, Sanz I. Advances in human B cell phenotypic profiling. Front Immunol 3. 2012; 302. DOI: 10.3389/fimmu.2012.00302.Khodadadi L, Cheng Q, Radbruch A, Hiepe F. The maintenance of memory plasma cells. Front Immunol 10. 2019; 721. DOI: 10.3389/fimmu.2019.00721.Khodadadi L, Cheng Q, Radbruch A, Hiepe F. The maintenance of memory plasma cells. Front Immunol 10. 2019; 721. DOI: 10.3389/fimmu.2019.00721.Pavlasova G, Mraz M. The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020; 105 (6): 1494–506. DOI: 10.3324/haematol.2019.243543.Pavlasova G, Mraz M. The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020; 105 (6): 1494–506. DOI: 10.3324/haematol.2019.243543.Palm AE, Henry C. Remembrance of things past: long-term B cell memory after infection and vaccination. Front Immunol. 2019; 10: 1787. DOI: 10.3389/fimmu.2019.01787.Palm AE, Henry C. Remembrance of things past: long-term B cell memory after infection and vaccination. Front Immunol. 2019; 10: 1787. DOI: 10.3389/fimmu.2019.01787.Luz EC, Damaris EL. "Introduction to T and B lymphocytes," in autoimmunity: from bench to bedside. El Rosario University Press, 2013.Luz EC, Damaris EL. "Introduction to T and B lymphocytes," in autoimmunity: from bench to bedside. El Rosario University Press, 2013.Adachi Y, Onodera T, Yamada Y, Daio R, Tsuiji M, Inoue T, et al. Distinct germinal center selection at local sites shapes memory B cell response to viral escape. J Exp Med. 2015; 212 (10), 1709–23. DOI: 10.1084/jem.20142284.Adachi Y, Onodera T, Yamada Y, Daio R, Tsuiji M, Inoue T, et al. Distinct germinal center selection at local sites shapes memory B cell response to viral escape. J Exp Med. 2015; 212 (10), 1709– 23. DOI: 10.1084/jem.20142284.Quinn JL, Kumar G, Agasing A, Ko RM, Axtell RC. Role of TFH cells in promoting T helper 17-induced neuroinflammation. Front Immunol. 2018; 9: 382. DOI: 10.3389/fimmu.2018.00382.Quinn JL, Kumar G, Agasing A, Ko RM, Axtell RC. Role of TFH cells in promoting T helper 17-induced neuroinflammation. Front Immunol. 2018; 9: 382. DOI: 10.3389/fimmu.2018.00382.Atisha-Fregoso Y, Zou YR, Diamond B. "B cells and generation of antibodies". In: Dubois' Lupus Erythematosus and Related Syndromes. Elsevier, 2019; 101–15.Atisha-Fregoso Y, Zou YR, Diamond B. "B cells and generation of antibodies". In: Dubois' Lupus Erythematosus and Related Syndromes. Elsevier, 2019; 101–15.Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018; 31 (3): 256–262. DOI: 10.1097/WCO.000000000000563.Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018; 31 (3): 256–262. DOI: 10.1097/WCO.000000000000563.Adler LN, Jiang W, Bhamidipati K, Millican M, Macaubas C, et al. The other function: class II-restricted antigen presentation by B cells. Front Immunol. 2017; 8: 319. DOI: 10.3389/fimmu.2017.00319.Adler LN, Jiang W, Bhamidipati K, Millican M, Macaubas C, et al. The other function: class II-restricted antigen presentation by B cells. Front Immunol. 2017; 8: 319. DOI: 10.3389/fimmu.2017.00319.Hausser-Kinzel S, Weber MS. The role of B cells and antibodies in multiple sclerosis, neuromyelitis optica, and related disorders. Front Immunol. 2019; 10: 201. DOI: 10.3389/fimmu.2019.00201.Hausser-Kinzel S, Weber MS. The role of B cells and antibodies in multiple sclerosis, neuromyelitis optica, and related disorders. Front Immunol. 2019; 10: 201. DOI: 10.3389/fimmu.2019.00201.Barr TA, Shen P, Brown S, Lampropoulou V, Roch T, Lawrie S, et al. B cell depletion therapy ameliorates autoimmune disease through ablation of IL6-producing B cells. J Exp Med. 2012; 209 (5): 1001–10. DOI: 10.1084/jem.20111675.Barr TA, Shen P, Brown S, Lampropoulou V, Roch T, Lawrie S, et al. B cell depletion therapy ameliorates autoimmune disease through ablation of IL6-producing B cells. J Exp Med. 2012; 209 (5): 1001–10. DOI: 10.1084/jem.20111675.Yu X, Graner M, Kennedy PGE, Liu Y. The role of antibodies in the pathogenesis of multiple sclerosis. Front Neurol. 2020; 11: 533388. DOI: 10.3389/fneur.2020.533388.Yu X, Graner M, Kennedy PGE, Liu Y. The role of antibodies in the pathogenesis of multiple sclerosis. Front Neurol. 2020; 11: 533388. DOI: 10.3389/fneur.2020.533388.Negron A, Stüve O, Forsthuber TG. Ectopic lymphoid follicles in multiple sclerosis: Centers for Disease Control. Front Neurol. 2020 Dec 8; 11: 607766. DOI: 10.3389/fneur.2020.607766.Negron A, Stüve O, Forsthuber TG. Ectopic lymphoid follicles in multiple sclerosis: Centers for Disease Control. Front Neurol. 2020 Dec 8; 11: 607766. DOI: 10.3389/fneur.2020.607766.Bell L, Lenhart A, Rosenwald A, Monoranu CM, Berberich-Siebelt F. Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells. Front Immunol. 2020 Jan 15; 10: 3090. DOI: 10.3389/fimmu.2019.03090.Bell L, Lenhart A, Rosenwald A, Monoranu CM, Berberich-Siebelt F. Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells. Front Immunol. 2020 Jan 15; 10: 3090. DOI: 10.3389/fimmu.2019.03090.Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23; 16 (1): 272. DOI: 10.1186/s12974-019-1674-2.Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23; 16 (1): 272. DOI: 10.1186/s12974-019-1674-2.Schwenkenbecher P, Konen FF, Wurster U, Jendretzky KF, Gingele S, Sühs KW, et al. The persisting significance of oligoclonal bands in the dawning era of kappa free light chains for the diagnosis of multiple sclerosis. Int J Mol Sci. 2018 Nov 29; 19 (12): 3796. DOI: 10.3390/ijms19123796.Schwenkenbecher P, Konen FF, Wurster U, Jendretzky KF, Gingele S, Sühs KW, et al. The persisting significance of oligoclonal bands in the dawning era of kappa free light chains for the diagnosis of multiple sclerosis. Int J Mol Sci. 2018 Nov 29; 19 (12): 3796. DOI: 10.3390/ijms19123796.Lefvert A, Link H. IgG production within the central nervous system: a critical review of proposed formulae. Ann Neurol. 1985; 17: 13–20. DOI: 10.1002/ana.410170105.Lefvert A, Link H. IgG production within the central nervous system: a critical review of proposed formulae. Ann Neurol. 1985; 17: 13–20. DOI: 10.1002/ana.410170105.Tintore M, Rovira À, Río J, Otero-Romero S, Arrambide G, Tur C, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain. 2015 Jul; 138 (Pt 7): 1863–74. DOI: 10.1093/brain/awv105.Tintore M, Rovira À, Río J, Otero-Romero S, Arrambide G, Tur C, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain. 2015 Jul; 138 (Pt 7): 1863–74. DOI: 10.1093/brain/awv105.Kuhle J, Disanto G, Dobson R, et al. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study. Mult Scler. 2015; 21 (8): 1013–24.Kuhle J, Disanto G, Dobson R, et al. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study. Mult Scler. 2015; 21 (8): 1013–24.Lebrun-Frenay C, Kantarci O, Siva A, Sormani MP, Pelletier D, Okuda DT. 10-year RISC study group on behalf of SFSEP, OFSEP. Radiologically isolated syndrome: 10-year risk estimate of a clinical event. Ann Neurol. 2020 Aug; 88 (2): 407–17. DOI: 10.1002/ana.25799.Lebrun-Frenay C, Kantarci O, Siva A, Sormani MP, Pelletier D, Okuda DT. 10-year RISC study group on behalf of SFSEP, OFSEP. Radiologically isolated syndrome: 10-year risk estimate of a clinical event. Ann Neurol. 2020 Aug; 88 (2): 407–17. DOI: 10.1002/ana.25799.Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020 Jun 26; 11: 501. DOI: 10.3389/fneur.2020.00501.Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020 Jun 26; 11: 501. DOI: 10.3389/fneur.2020.00501.Greenfield AL, Hauser SL. B-cell therapy for multiple sclerosis: entering an era. Ann Neurol. 2018 Jan; 83 (1): 13–26. DOI: 10.1002/ana.25119.Greenfield AL, Hauser SL. B-cell therapy for multiple sclerosis: entering an era. Ann Neurol. 2018 Jan; 83 (1): 13–26. DOI: 10.1002/ana.25119.Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. E Bio Medicine. 2017; 16: 41–50.Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. E Bio Medicine. 2017; 16: 41–50.Bose T. Role of immunological memory cells as a therapeutic target in multiple sclerosis. Brain Sci. 2017; 7 (11): E148.Bose T. Role of immunological memory cells as a therapeutic target in multiple sclerosis. Brain Sci. 2017; 7 (11): E148.Ciron J, Audoin B, Bourre B, Brassat D, Durand-Dubief F, Laplaud D, et al. NOMADMUS group, under the aegis of OFSEP, SFSEP. Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders Rev Neurol (Paris). 2018; 174 (4): 255–64.Ciron J, Audoin B, Bourre B, Brassat D, Durand-Dubief F, Laplaud D, et al. NOMADMUS group, under the aegis of OFSEP, SFSEP. Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders Rev Neurol (Paris). 2018; 174 (4): 255–64.Kim SH, Kim W, Li XF, Jung IJ, Kim HJ. Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol. 2011; 68, 1412–20.Kim SH, Kim W, Li XF, Jung IJ, Kim HJ. Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol. 2011; 68, 1412–20.Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, Hwang SH, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 72: 989–95.Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, Hwang SH, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 72: 989–95.Kim SH, Huh SY, LeeSJ, Joung A, Kim HJ. A5-yearfollow-up ofrituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013; 70: 1110–7.Kim SH, Huh SY, LeeSJ, Joung A, Kim HJ. A5-yearfollow-up ofrituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013; 70: 1110–7.Thompson SA, Jones JL, Cox AL, et al. B-cell reconstitution and BAFF after alemtuzumab (CAMPATH-1H) treatment of multiple sclerosis. J Clin Immunol. 2010; 30: 99–105.Thompson SA, Jones JL, Cox AL, et al. B-cell reconstitution and BAFF after alemtuzumab (CAMPATH-1H) treatment of multiple sclerosis. J Clin Immunol. 2010; 30: 99–105.Duddy M, Niino M, Adatia F, et al. Distincteffectorcytokineprofil esofmemoryand naive human B cell subsets and implication in multiple sclerosis. J Immunol. 2007; 178: 6092–9.Duddy M, Niino M, Adatia F, et al. Distincteffectorcytokineprofil esofmemoryand naive human B cell subsets and implication in multiple sclerosis. J Immunol. 2007; 178: 6092–9.Giovannoni G, Cohen JA, Coles AJ, Hartung HP, Havrdova E, Selmaj KW, et al. CARE-MS II Investigators. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016 Nov 8; 87 (19): 1985–92.Giovannoni G, Cohen JA, Coles AJ, Hartung HP, Havrdova E, Selmaj KW, et al. CARE-MS II Investigators. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016 Nov 8; 87 (19): 1985–92.Van Oosten BW, Lai M, Hodgkinson S, et al. Treatmentofmultiple sclerosiswith the monoclonal anti-CD4 antibody cM-T412:results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial. Neurology. 1997; 49: 351–7.Van Oosten BW, Lai M, Hodgkinson S, et al. Treatmentofmultiple sclerosiswith the monoclonal anti-CD4 antibody cM-T412:results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial. Neurology. 1997; 49: 351–7.Ceronie B, Jacobs BM, Baker D, Dubuisson N, Mao Z, Ammoscato F, et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018 May; 265 (5): 1199–209.Ceronie B, Jacobs BM, Baker D, Dubuisson N, Mao Z, Ammoscato F, et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018 May; 265 (5): 1199–209.Giovannoni G, Cohen JA, Coles AJ, Hartung HP, Havrdova E, Selmaj KW, et al. CARE-MS II Investigators. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016 Nov 8; 87 (19): 1985–92.Giovannoni G, Cohen JA, Coles AJ, Hartung HP, Havrdova E, Selmaj KW, et al. CARE-MS II Investigators. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology. 2016 Nov 8; 87 (19): 1985–92.Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, et al. CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12; 89 (11): 1107–16. Neurology. 2018 Apr 17; 90 (16): 755.Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, et al. CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12; 89 (11): 1107–16. Neurology. 2018 Apr 17; 90 (16): 755.Genovese MC, Kaine JL, Lowenstein MB, et al. Ocrelizumab, a humanized antiCD20 monoclonalantibody, inthe treatment of patients with rheumatoidarthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008; 58: 2652–61.Genovese MC, Kaine JL, Lowenstein MB, et al. Ocrelizumab, a humanized antiCD20 monoclonalantibody, inthe treatment of patients with rheumatoidarthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008; 58: 2652–61.Kuerten S, Jackson LJ, Kaye J, Vollmer TL. Impact of glatiramer acetate on B cell-mediated pathogenesis of multiple sclerosis. CNS Drugs. 2018; 32 (11): 1039–51.Kuerten S, Jackson LJ, Kaye J, Vollmer TL. Impact of glatiramer acetate on B cell-mediated pathogenesis of multiple sclerosis. CNS Drugs. 2018; 32 (11): 1039–51.Begum-Haque S, Christy M, Ochoa-Reparaz J, Nowak EC, Mielcarz D, Haque A, et al. Augmentation of regulatory B cell activity in experimental allergic encephalomyelitis by glatiramer acetate. J Neuroimmunol. 2011 Mar; 232 (0): 136–44.Begum-Haque S, Christy M, Ochoa-Reparaz J, Nowak EC, Mielcarz D, Haque A, et al. Augmentation of regulatory B cell activity in experimental allergic encephalomyelitis by glatiramer acetate. J Neuroimmunol. 2011 Mar; 232 (0): 136–44.Ireland SJ, Guzman AA, O Brien DE, Hughes S, Greenberg B, Flores A, et al. The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. JAMA Neurol. 2014 Nov; 71 (11): 1421–8.Ireland SJ, Guzman AA, O Brien DE, Hughes S, Greenberg B, Flores A, et al. The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. JAMA Neurol. 2014 Nov; 71 (11): 1421–8.Schubert RD, Hu Y, Kumar G, Szeto S, Abraham P, Winderl J, et al. Interferon-β treatment requires B cells for efficacy in neuroautoimmunity. J Immunol. 2015 Mar 1; 194 (5): 2110–6.Schubert RD, Hu Y, Kumar G, Szeto S, Abraham P, Winderl J, et al. Interferon-β treatment requires B cells for efficacy in neuroautoimmunity. J Immunol. 2015 Mar 1; 194 (5): 2110–6.Ramgolam VS, Sha Y, Marcus KL, Choudhary N, Troiani L, Chopra M, et al. B cells as a therapeutic target for IFN-β in relapsing–remitting multiple sclerosis. J Immunol. 2011; 186 (7): 4518–26.Ramgolam VS, Sha Y, Marcus KL, Choudhary N, Troiani L, Chopra M, et al. B cells as a therapeutic target for IFN-β in relapsing– remitting multiple sclerosis. J Immunol. 2011; 186 (7): 4518–26.Sabatino JJ, Zamvil SS, Hauser SL. B-cell therapies in multiple sclerosis. Cold Spring Harb Perspect Med. 2019 Feb; 9 (2): a032037.Sabatino JJ, Zamvil SS, Hauser SL. B-cell therapies in multiple sclerosis. Cold Spring Harb Perspect Med. 2019 Feb; 9 (2): a032037.Lehmann-Horn K, Kinzel S, Weber MS. Deciphering the role of B cells in multiple sclerosis-towards specific targeting of pathogenic function. Int J Mol Sci. 2017 Oct; 18 (10): 2048.Lehmann-Horn K, Kinzel S, Weber MS. Deciphering the role of B cells in multiple sclerosis-towards specific targeting of pathogenic function. Int J Mol Sci. 2017 Oct; 18 (10): 2048.Gregson A, Thompson K, Tsirka SE, Selwood DL. Emerging small-molecule treatments for multiple sclerosis: focus on B cells. F1000Res. 2019; 8: F1000 Faculty Rev-245.Gregson A, Thompson K, Tsirka SE, Selwood DL. Emerging small-molecule treatments for multiple sclerosis: focus on B cells. F1000Res. 2019; 8: F1000 Faculty Rev-245.Braley TJ, Segal BM. B-cell targeting agents in the treatment of multiple sclerosis. Curr Treat Options Neurol. 2013 Jun; 15 (3): 259–69.Braley TJ, Segal BM. B-cell targeting agents in the treatment of multiple sclerosis. Curr Treat Options Neurol. 2013 Jun; 15 (3): 259–69.Traub JW, Häusser-Kinzel S, Weber MS. Differential effects of MS therapeutics on B cells-implications for their use and failure in AQP4-positive NMOSD patients. Int J Mol Sci. 2020 Jul; 21 (14): 5021.Traub JW, Häusser-Kinzel S, Weber MS. Differential effects of MS therapeutics on B cells-implications for their use and failure in AQP4-positive NMOSD patients. Int J Mol Sci. 2020 Jul; 21 (14): 5021.Claes N, Fraussen J, Stinissen P, Hupperts R, Somers V. B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions. Front Immunol. 2015; 6: 642.Claes N, Fraussen J, Stinissen P, Hupperts R, Somers V. B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions. Front Immunol. 2015; 6: 642.Traub JW, Pellkofer HL, Grondey K, Seeger I, Rowold C, Brück W, et al. Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients. J Neuroinflammation. 2019; 16: 228.Traub JW, Pellkofer HL, Grondey K, Seeger I, Rowold C, Brück W, et al. Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients. J Neuroinflammation. 2019; 16: 228.Häusler D, Häusser-Kinzel S, Feldmann L, Torke S, Lepennetier G, Bernard CCA, et al. Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease. Proc Natl Acad Sci USA. 2018 Sep 25; 115 (39): 9773–8.Häusler D, Häusser-Kinzel S, Feldmann L, Torke S, Lepennetier G, Bernard CCA, et al. Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease. Proc Natl Acad Sci USA. 2018 Sep 25; 115 (39): 9773–8.Fernández-Velasco JI, Kuhle J, Monreal E, et al. Effect of ocrelizumab in blood leukocytes of patients with primary progressive MS. Neurol Neuroimmunol Neuroinflamm. 2021 Mar; 8 (2): e940.Fernández-Velasco JI, Kuhle J, Monreal E, et al. Effect of ocrelizumab in blood leukocytes of patients with primary progressive MS. Neurol Neuroimmunol Neuroinflamm. 2021 Mar; 8 (2): e940.

The authors declare that there are no conflicts of interest present.