Update on the autoimmune pathology of multiple sclerosis: B-cells as disease-drivers and therapeutic targets

European Neurology

Volumn 73, Issue 3-4, 2015, Pages 238-246

  Von Büdingen, H Christian ^a   Palanichamy, Arumugam ^a   Lehmann Horn, Klaus ^a   Michel, Brady A ^a   Zamvil, Scott S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

B cell depleting therapy; B cells; Multiple sclerosis

Indexed keywords

B CELL ACTIVATING FACTOR RECEPTOR; CD19 ANTIBODY; CD19 ANTIGEN; CD20 ANTIBODY; CYTOKINE RECEPTOR ANTAGONIST; RITUXIMAB; IMMUNOLOGIC FACTOR;

ANTIBODY PRODUCTION; ARTICLE; AUTOIMMUNE DISEASE; B LYMPHOCYTE; CELL COMPARTMENTALIZATION; CENTRAL NERVOUS SYSTEM; HUMAN; IMMUNOPATHOLOGY; LYMPHOCYTE FUNCTION; MULTIPLE SCLEROSIS; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; ADULT; ANIMAL; IMMUNOLOGY; YOUNG ADULT;

ADULT; ANIMALS; B-LYMPHOCYTES; HUMANS; IMMUNOLOGIC FACTORS; MULTIPLE SCLEROSIS; RITUXIMAB; YOUNG ADULT;

EID: 84926190925     PISSN: 00143022     EISSN: 14219913     Source Type: Journal    
DOI: 10.1159/000377675     Document Type: Article

References (81)

1. Compston A, Coles A: Multiple sclerosis. Lancet 2008; 372: 1502-1517.
2. Orton SM, Herrera BM, Yee IM, et al: Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006; 5: 932-936.
3. Hauser SL, Oksenberg JR: The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2006; 52: 61-76.
4. Bar-Or A, Calabresi PA, Arnold D, et al: Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63: 395-400.
5. Hauser SL, Waubant E, Arnold DL, et al: Bcell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358: 676-688.
6. Kappos L, Li D, Calabresi PA, et al: Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 2011; 378: 1779-1787.
7. Sorensen PS, Lisby S, Grove R, et al: Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology 2014; 82: 573-581.
8. Genain CP, Nguyen MH, Letvin NL, et al: Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J Clin Invest 1995; 96: 2966-2974.
9. Linington C, Engelhardt B, Kapocs G, Lassman H: Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody. J Neuroimmunol 1992; 40: 219-224.
10. Lyons JA, Ramsbottom MJ, Cross AH: Critical role of antigen-specific antibody in experimental autoimmune encephalomyelitis induced by recombinant myelin oligodendrocyte glycoprotein. Eur J Immunol 2002; 32: 1905-1913.
11. Schluesener HJ, Sobel RA, Linington C, Weiner HL: A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol 1987; 139: 4016-4021.
12. Lyons JA, San M, Happ MP, Cross AH: B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide. Eur J Immunol 1999; 29: 3432-3439.
13. Molnarfi N, Schulze-Topphoff U, Weber MS, et al: MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelinspecific antibodies. J Exp Med 2013; 210: 2921-2937.
14. Weber MS, Prod'homme T, Patarroyo JC, et al: B-cell activation influences T-cell polarization and outcome of anti-CD20 b-cell depletion in central nervous system autoimmunity. Ann Neurol 2010; 68: 369-383.
15. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC: Predominant autoantibody production by early human B cell precursors. Science 2003; 301: 1374-1377.
16. Mouquet H, Scheid JF, Zoller MJ, et al: Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. Nature 2010; 467: 591-595.
17. Kinnunen T, Chamberlain N, Morbach H, et al: Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest 2013; 123: 2737-2741.
18. Stern JN, Yaari G, Vander Heiden JA, et al: B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med 2014; 6: 248ra107.
19. Berer K, Mues M, Koutrolos M, et al: Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011; 479: 538-541.
20. Bar-Or A, Oliveira EM, Anderson DE, et al: Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state. J Immunol 2001; 167: 5669-5677.
21. Duddy M, Niino M, Adatia F, et al: Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 2007; 178: 6092-6099.
22. Harp CT, Ireland S, Davis LS, et al: Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Eur J Immunol 2010; 40: 2942-2956.
23. Roll P, Palanichamy A, Kneitz C, Dorner T, Tony HP: Regeneration of B cell subsets after transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Arthritis Rheum 2006; 54: 2377-2386.
24. Hauser S, Li D, Calabresi P, et al. (eds): Week 144 Results of a Phase II, Randomized, Multicenter Trial Assessing the Safety and Efficacy of Ocrelizumab in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) (S31.004). San Diego, CA, 2013.
25. Barr TA, Shen P, Brown S, et al: B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med 2012; 209: 1001-1010.
26. Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC: Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54: 613-620.
27. Bar-Or A, Fawaz L, Fan B, et al: Abnormal Bcell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67: 452-461.
28. Correale J, Fiol M, Gilmore W: The risk of relapses in multiple sclerosis during systemic infections. Neurology 2006; 67: 652-659.
29. Buljevac D, Flach HZ, Hop WC, et al: Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 2002; 125: 952-960.
30. Blair PA, Norena LY, Flores-Borja F, et al: CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 2010; 32: 129-140.
31. Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF: Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest 2008; 118: 3420-3430.
32. Iwata Y, Matsushita T, Horikawa M, et al: Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011; 117: 530-541.
33. Yoshizaki A, Miyagaki T, DiLillo DJ, et al: Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012; 491: 264-268.
34. Lehmann-Horn K, Schleich E, Hertzenberg D, et al: Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders. J Neuroinflammation 2011; 8: 146.
35. Palanichamy A, Apeltsin L, Kuo TC, et al: Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis. Sci Transl Med 2014; 6: 248ra106.
36. von Büdingen HC, Kuo TC, Sirota M, et al: B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 2012; 122: 4533-4543.
37. Bankoti J, Apeltsin L, Hauser SL, et al: In multiple sclerosis, oligoclonal bands connect to peripheral B-cell responses. Ann Neurol 2014; 75: 266-276.
38. Frischer JM, Bramow S, Dal-Bianco A, et al: The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009; 132: 1175-1189.
39. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F: Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14: 164-174.
40. Howell OW, Reeves CA, Nicholas R, et al: Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011; 134: 2755-2771.
41. Magliozzi R, Howell OW, Reeves C, et al: A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68: 477-493.
42. Magliozzi R, Columba-Cabezas S, Serafini B, Aloisi F: Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 2004; 148: 11-23.
43. Krumbholz M, Theil D, Cepok S, et al: Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 2006; 129: 200-211.
44. Krumbholz M, Theil D, Derfuss T, et al: BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 2005; 201: 195-200.
45. Baranzini SE, Jeong MC, Butunoi C, Murray RS, Bernard CC, Oksenberg JR: B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions. J Immunol 1999; 163: 5133-5144.
46. Owens GP, Ritchie AM, Burgoon MP, Williamson RA, Corboy JR, Gilden DH: Singlecell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J Immunol 2003; 171: 2725-2733.
47. Qin Y, Duquette P, Zhang Y, Talbot P, Poole R, Antel J: Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998; 102: 1045-1050.
48. Sandberg-Wollheim M, Turesson I: Lymphocyte subpopulations in the cerebrospinal fluid and peripheral blood in patients with multiple sclerosis. Scand J Immunol 1975; 4: 831-836.
49. Ritchie AM, Gilden DH, Williamson RA, et al: Comparative analysis of the CD19+ and CD138+ cell antibody repertoires in the cerebrospinal fluid of patients with multiple sclerosis. J Immunol 2004; 173: 649-656.
50. Colombo M, Dono M, Gazzola P, et al: Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients. J Immunol 2000; 164: 2782-2789.
51. Smith-Jensen T, Burgoon MP, Anthony J, Kraus H, Gilden DH, Owens GP: Comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains reveals an antigen-driven response. Neurology 2000; 54: 1227-1232.
52. Beltrán E, Obermeier B, Moser M, et al: Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation. Brain 2014; 137: 2703-2714.
53. Lovato L, Willis SN, Rodig SJ, et al: Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis. Brain 2011; 134: 534-541.
54. Obermeier B, Lovato L, Mentele R, et al: Related B cell clones that populate the CSF and CNS of patients with multiple sclerosis produce CSFimmunoglobulin. J Neuroimmunol 2011; 233: 245-248.
55. Corcione A, Casazza S, Ferretti E, et al: Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci U S A 2004; 101: 11064-11069.
56. Obermeier B, Mentele R, Malotka J, et al: Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nat Med 2008; 14: 688-693.
57. von Büdingen HC, Gulati M, Kuenzle S, Fischer K, Rupprecht TA, Goebels N: Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce 'oligoclonal bands'. J Neuroimmunol 2010; 218: 134-139.
58. Cepok S, Rosche B, Grummel V, et al: Shortlived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain 2005; 128: 1667-1676.
59. Haas J, Bekeredjian-Ding I, Milkova M, et al: B cells undergo unique compartmentalized redistribution in multiple sclerosis. J Autoimmun 2011; 37: 289-299.
60. Kostulas VK, Link H, Lefvert AK: Oligoclonal IgG bands in cerebrospinal fluid. Principles for demonstration and interpretation based on findings in 1114 neurological patients. Arch Neurol 1987; 44: 1041-1044.
61. Villar LM, Masjuan J, Gonzalez-Porque P, et al: Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS. Neurology 2002; 59: 555-559.
62. Sindic CJ, Monteyne P, Laterre EC: Occurrence of oligoclonal IgM bands in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study. J Neurol Sci 1994; 124: 215-219.
63. 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: 707-717.
64. Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC: Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 2010; 133: 349-361.
65. Robak T, Robak E: New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid malignancies. BioDrugs 2011; 25: 13-25.
66. Palanichamy A, Jahn S, Nickles D, et al: Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol 2014; 193: 580-586.
67. Gong Q, Ou Q, Ye S, et al: Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J Immunol 2005; 174: 817-826.
68. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA: Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006; 180: 63-70.
69. Brinkman IH, van de Laar MA, Jansen TL, van Roon EN: The potential risk of infections during (prolonged) rituximab therapy in rheumatoid arthritis. Expert Opin Drug Saf 2011; 10: 715-726.
70. Hultin LE, Hausner MA, Hultin PM, Giorgi JV: CD20 (pan-B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes. Cytometry 1993; 14: 196-204.
71. Wilk E, Witte T, Marquardt N, et al: Depletion of functionally active CD20+ T cells by rituximab treatment. Arthritis Rheum 2009; 60: 3563-3571.
72. Eggleton P, Bremer E, Tarr JM, et al: Frequency of Th17 CD20+ cells in the peripheral blood of rheumatoid arthritis patients is higher compared to healthy subjects. Arthritis Res Ther 2011; 13:R208.
73. Herbst R, Wang Y, Gallagher S, et al: B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther 2010; 335: 213-222.
74. Tedder TF: CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol 2009; 5: 572-577.
75. Yazawa N, Hamaguchi Y, Poe JC, Tedder TF: Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease. Proc Natl Acad Sci U S A 2005; 102: 15178-15183.
76. Munn DH, Sharma MD, Hou D, et al: Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004; 114: 280-290.
77. Carter RH, Zhao H, Liu X, et al: Expression and occupancy of BAFF-R on B cells in systemic lupus erythematosus. Arthritis Rheum 2005; 52: 3943-3954.
78. Ng LG, Sutherland AP, Newton R, et al: B cellactivating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol 2004; 173: 807-817.
79. Hartung HP, Kieseier BC: Atacicept: targeting B cells in multiple sclerosis. Ther Adv Neurol Disord 2010; 3: 205-216.
80. Sasaki Y, Casola S, Kutok JL, Rajewsky K, Schmidt-Supprian M: TNF family member B cell-activating factor (BAFF) receptor-dependent and-independent roles for BAFFin B cell physiology. J Immunol 2004; 173: 2245-2252.
81. Kim SS, Richman DP, Zamvil SS, Agius MA: Accelerated central nervous system autoimmunity in BAFF-receptor-deficient mice. J Neurol Sci 2011; 306: 9-15.