B-cell function in CNS inflammatory demyelinating disease: A complexity of roles and a wealth of possibilities

Expert Review of Clinical Immunology

Volumn 3, Issue 4, 2007, Pages 565-578

  Fillatreau, Simon ^a   Anderton, Stephen M ^b  

^a DEUTSCHES RHEUMA FORSCHUNGSZENTRUM   (Germany)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; ANTIBODY CONJUGATE; AUTOANTIBODY; AUTOANTIGEN; BETA INTERFERON; IMMUNOGLOBULIN; IMMUNOGLOBULIN D ANTIBODY MYELIN BASIC PROTEIN CONJUGATE; IMMUNOGLOBULIN G; INTERLEUKIN 10; MYELIN ASSOCIATED GLYCOPROTEIN; MYELIN BASIC PROTEIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MYELIN PROTEIN; OLIGOCLONAL BAND; PLACEBO; RITUXIMAB; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; AUTOIMMUNE HEMOLYTIC ANEMIA; B LYMPHOCYTE; CELL DIFFERENTIATION; CELL INFILTRATION; CELLULAR DISTRIBUTION; CERVICAL LYMPH NODE; CLINICAL TRIAL; DEMYELINATION; DRUG DOSAGE FORM COMPARISON; ENCEPHALOMYELITIS; GENE THERAPY; HUMAN; HUMORAL IMMUNITY; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNE DYSREGULATION; IMMUNOLOGICAL TOLERANCE; LYMPHOCYTE FUNCTION; LYMPHOCYTIC INFILTRATION; MULTIPLE SCLEROSIS; MYELIN SHEATH; MYELOOPTIC NEUROPATHY; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NONHUMAN; PLASMA CELL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN SYNTHESIS; REGULATORY MECHANISM; REVIEW;

EID: 34447635715     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/1744666X.3.4.565     Document Type: Review

References (159)

1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N. Engl. J. Med. 343(13), 938-952(2000).
2. 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. 47(6), 707-717(2000).
3. Zamvil S, Nelson P, Trotter J et al. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317(6035), 355-358(1985).
4. Blennow K, Fredman P. Wallin A et al. Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis. J. Neurol. Sci. 121(1), 90-96 (1994).
5. Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult. Scler. 4(3), 111-117 (1998).
6. Correale J, de los Milagros Bassani Molinas M. Oligoclonal bands and antibody responses in multiple sclerosis. J. Neurol. 249(4), 375-389 (2002).
7. Lee KH, Hashimoto SA, Hooge JP et al. Magnetic resonance imaging of the head in the diagnosis of multiple sclerosis: a prospective 2-year follow-up with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 41(5), 657-660 (1991).
8. Berger T, Rubner P, Schautzer F et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N. Engl. J. Med. 349(2), 139-145 (2003).
9. Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N. Engl. J. Med. 346(3), 158-164 (2002).
10. Thompson EJ, Kaufmann P, Rudge P. Sequential changes in oligoclonal patterns during the course of multiple sclerosis. J. Neurol. Neurosurg. Psychiatr. 46(6), 547-550 (1983).
11. Tourtellotte WW, Ma BI. Multiple sclerosis: the blood-brain-barrier and the measurement of de novo central nervous system IgG synthesis. Neurology 28(9 Pt 2), 76-83 (1978).
12. Walsh MJ, Tourtellotte WW, Roman J, Dreyer W. Immunoglobulin G, A, and M - clonal restriction in multiple sclerosis cerebrospinal fluid and serum - analysis by two-dimensional electrophoresis. Clin. Immunol. Immunopathol. 35(3), 313-327 (1985).
13. + regulatory T cells in patients with multiple sclerosis. J Fxp. Med. 199(7), 971-979 (2004).
14. Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin. Invest. 116(12), 3252-3257(2006).
15. Cruz M, Olsson T, Ernerudh J, Hojeberg B, Link H. Immunoblot detection of oligoclonal anti-myelin basic protein IgG antibodies in cerebrospinal fluid in multiple sclerosis. Neurology 37(9), 1515-1519 (1987).
16. Garbay B, Heape AM, Sargueil F, Cassagne C. Myelin synthesis in the peripheral nervous system. Prog. Neurobiol. 61(3), 267-304 (2000).
17. Stoffel W, Hillen H, Giersiefen H. Structure and molecular arrangement of proteolipid protein of central nervous system myelin. Proc. Natl Acad. Sci. USA 81(16), 5012-5016 (1984).
18. Omlin FX, Webster HD, Palkovits CG, Cohen SR. Immunocytochemical localization of basic protein in major dense line regions of central and peripheral myelin. J. Cell Biol. 95(1), 242-248 (1982).
19. Roach A, Takahashi N, Pravtcheva D, Ruddle F, Hood L. Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42(1), 149-155 (1985).
20. Sprinkle TJ. 2′, 3′ -cyclic nucleotide 3′-phosphodiesterase, an oligodendrocyte-Schwann cell and myelin-associated enzyme of the nervous system. Crit. Rev. Neurobiol. 4(3), 235-301 (1989).
21. Johns TG, Bernard CC. The structure and function of myelin oligodendrocyte glycoprotein. J. Neurochem. 72(1), 1-9 (1999).
22. Linnington C, Webb M, Woodhams PL. A novel myelin-associated glycoprotein defined by a mouse monoclonal antibody. J. Neuroimmunol. 6(6), 387-396 (1984).
23. Kuhle J, Pohl C, Mehling M et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N. Engl. J. Med. 356(4), 371-378 (2007).
24. Lalive PH, Menge T, Delarasse C et al. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc. Natl Acad. Sci. USA 103(7), 2280-2285 (2006).
25. Egg R, Reindl M, Deisenhammer F, Linington C, Berger T. Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Mult Scler. 7(5), 285-289 (2001).
26. Gerritse K, Deen C, Fasbender M, Ravid R, Boersma W, Claassen E. The involvement of specific anti myelin basic protein antibody-forming cells in multiple sclerosis immunopathology. J. Neuroimmunol. 49(1-2),153-159 (1994).
27. Olsson T, Baig S, Hojeberg B, Link H. Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis. Ann. Neurol. 27(2), 132-136 (1990).
28. Reindl M, Linington C, Brehm U et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122(Pt 11), 2047-2056(1999).
29. Boggs JM. Myelin basic protein: a multifunctional protein. Cell. Mol. Life Sci. 63(17), 1945-1961 (2006).
30. Wood DD, Bilbao JM, O'Connors P, Moscarello MA. Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein. Ann. Neurol. 40(1), 18-24 (1996).
31. Musse AA, Boggs JM, Harauz G. Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope. Proc. Natl Acad. Sci. USA 103(12), 4422-4427 (2006).
32. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 60(5), 848-853 (2003).
33. Misu T, Fujihara K, Nakashima I et al. Pure optic-spinal form of multiple sclerosis in Japan. Brain 125(Pt 11), 2460-2468 (2002).
34. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 202(4), 473-477 (2005).
35. Lennon VA, Wingerchuk DM, Kryzer TJ et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451), 2106-2112(2004).
36. Warren KG, Catz I. Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and multiple sclerosis cerebrospinal fluid. J. Neurol. Sci. 121(1), 66-73 (1994).
37. Baig S, Olsson T, Yu-Ping J, Hojeberg B, Cruz M, Link H. Multiple sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid. Scand. J. Immunol. 33(1), 73-79 (1991).
38. Walsh MJ, Murray JM. Dual implication of 2′, 3′ -cyclic nucleotide 3′ phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis. J. Clin. Invest. 101(9), 1923-1931 (1998).
39. Eikelenboom MJ, Petzold A, Lazeron RH et al. Multiple sclerosis: neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology 60(2), 219-223 (2003).
40. Williamson RA, Burgoon MP. Owens GP et al. Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis. Proc. Natl Acad. Sci. USA 98(4), 1793-1798 (2001).
41. Menge T, Lalive PH, von Budingen HC, Cree B, Hauser SL, Genain CP. Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis. J. Allergy Clin. Immunol. 116(2), 453-459 (2005).
42. Hansen K, Cruz M, Link H. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J. Infect. Dis. 161(6), 1194-1202 (1990).
43. Hangartner L, Zinkernagel RM, Hengartner H. Antiviral antibody responses: the two extremes of a wide spectrum. Nat. Rev. Immunol. 6(3), 231-243 (2006).
44. Zhou D, Srivastava R, Nessler S et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc. Natl Acad. Sci. USA 103(50), 19057-19062(2006).
45. Marta CB, Oliver AR, Sweet RA, Pfeiffer SE, Ruddle NH. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proc. Natl Acad. Sci. USA 102(39), 13992-13997 (2005).
46. Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. 5(2), 170-175 (1999).
47. Raine CS, Cannella B, Hauser SL, Genain CP. Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen-specific antibody mediation. Ann. Neurol. 46(2), 144-160 (1999).
48. 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. 139(12), 4016-4021 (1987).
49. 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. 32(7), 1905-1913 (2002).
50. Genain CP, Nguyen MH, Letvin NL et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J. Clin. Invest. 96(6), 2966-2974 (1995).
51. Storch MK, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H. Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann. Neurol. 43(4), 465-471(1998).
52. Piddlesden SJ, Lassmann H, Zimprich F, Morgan BP, Linington C. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am. J. Pathol. 143(2), 555-564 (1993).
53. Marta CB, Taylor CM, Coetzee T et al. Antibody cross-linking of myelin oligodendrocyte glycoprotein leads to its rapid repartitioning into detergent-insoluble fractions, and altered protein phosphorylation and cell morphology. J. Neurosci. 23(13), 5461-5471 (2003).
54. Mithen FA, Agrawal. HC, Fishman MA, Eylar EH, Bunge RP. Studies with antisera against peripheral nervous system myelin and myelin basic proteins. II. Immunohistochemical studies in cultures of rat dorsal root ganglion neurons and Schwann cells. Brain Res. 250(2), 333-343 (1982).
55. Mithen FA, Agrawal HC, Eylar EH, Fishman MA, Blank W, Bunge RP. Studies with antisera against peripheral nervous system myelin and myelin basic proteins. I. Effects of antiserum upon living cultures of nervous tissue. Brain Res. 250(2), 321-331 (1982).
56. Robbie-Ryan M, Tanzola MB, Secor VH, Brown MA. Cutting edge: both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephatomyelitis disease severity. J. Immunol. 170(4), 1630-1634 (2003).
57. Lucchinetti CF, Mandler RN, McGavern D et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 125(Pt 7), 1450-1461 (2002).
58. Keegan M, Konig F, McClelland R et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 366(9485), 579-582 (2005).
59. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64(7), 1270-1272(2005).
60. Bettelli E, Pagany M, Weiner HL, Linington C, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J. Exp. Med. 197(9), 1073-1081 (2003).
61. Litzenburger T, Fassler R, Bauer J et al. B lymphocytes producing demyelinating autoantibodies: development and function in gene-targeted transgenic mice. J. Exp. Med. 188(1), 169-180 (1998).
62. Krishnamoorthy G, Lassmann H, Wekerle H, Holz A. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin. Invest. 116(9), 2385-2392 (2006).
63. Bettelli E, Baeten D, Jager A, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice. J. Clin. Invest. 116(9), 2393-2402 (2006).
64. Qin Y, Duquette P. Zhang Y et al. 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. 83(7), 1081-1088 (2003).
65. Owens GP, Ritchie AM, Burgoon MP, Williamson RA, Corboy JR, Gilden DH. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J. Immunol. 171(5), 2725-2733 (2003).
66. Esiri MM. Immunoglobulin-containing cells in multiple-sclerosis plaques. Lancet 2(8036), 478 (1977).
67. + cell antibody repertoires in the cerebrospinal fluid of patients with multiple sclerosis. J. Immunol. 173(1), 649-656(2004).
68. 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. USA 101 (30), 11064-11069 (2004).
69. 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. 14(2), 164-174 (2004).
70. Kim HJ, Krenn V, Steinhauser G, Berek C. Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J. Immunol. 162(5), 3053-3062 (1999).
71. Cepok S, Rosche B, Grummel V et al. Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain 128(Pt 7), 1667-1676(2005).
72. Odendahl M, Mei H, Hoyer BF et al. Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood 105(4), 1614-1621 (2005).
73. O'Connor BP, Raman VS, Erickson LD et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J. Exp. Med. 199(1), 91-98 (2004).
74. 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. 201(2),195-200 (2005).
75. Cassese G, Arce S, Hauser AE et al. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J. Immunol. 171 (4), 1684-1690(2003).
76. 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. 180(1-2), 63-70 (2006).
77. Monson NL, Cravens PD, Frohman EM, Hawker K, Racke MK. Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch. Neurol. 62(2), 258-264 (2005).
78. Streilein JW, Niederkorn JY, Shadduck JA. Systemic immune unresponsiveness induced in adult mice by anterior chamber presentation of minor histocompatibility antigens. J. Exp. Med. 152(4), 1121-1125 (1980).
79. Ksander BR, Streilein JW. Failure of infiltrating precursor cytotoxic T cells to acquire direct cytotoxic function in immunologically privileged sites. J. Immunol. 145(7), 2057-2063 (1990).
80. Niederkorn JY, Streilein JW. Analysis of antibody production induced by allogeneic tumor cells inoculated into the anterior chamber of the eye. Transplantation 33(6), 573-577 (1982).
81. Harling-Berg CJ, Knopf PM, Cserr HF. Myelin basic protein infused into cerebrospinal fluid suppresses experimental autoimmune encephalomyelitis. J. Neuroimmunol. 35(1-3), 45-51 (1991).
82. Knopf PM, Harling-Berg CJ, Cserr HF et al. Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells. J. Immunol. 161(2), 692-701(1998).
83. Hatterer E, Davoust N, Didier-Bazes M et al. How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes. Blood 107(2), 806-812 (2006).
84. Harling-Berg C, Knopf PM, Merriam J, Cserr HF. Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid. J. Neuroimmunol. 25(2-3), 185-193 (1989).
85. Wolf SD, Dittel BN, Hardardottir F, Janeway CA Jr. Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J. Exp. Med. 184(6), 2271-2278(1996).
86. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3(10), 944-950 (2002).
87. Kennedy MK, Torrance DS, Picha KS, Mohler KM. Analysis of cytokine mRNA expression in the CNS of mice with experimental autoinimune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J. Immunol. 149(7), 2496-2505 (1992).
88. Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK. IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J. Immunol. 161(7), 3299-3306(1998).
89. Perrella O, Sbreglia C, Perrella M et al. Interleukin-10 and tumor necrosis factor-α: model of immunomodulation in multiple sclerosis. Neurol. Res. 28(2), 193-195 (2006).
90. Navikas V, Link J, Palasik W et al. Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis. Scand. J. Immunol. 41(2), 171-178 (1995).
91. Rudick RA, Ransohoff RM, Peppler R, VanderBrug Medendorp, S, Lehmann P, Alam J. Interferon β induces interleukin-10 expression: relevance to multiple sclerosis. Ann. Neurol. 40(4), 618-627 (1996).
92. Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleuki 10-producing B cells. J. Exp. Med. 197(4), 489-501(2003).
93. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16(2), 219-230 (2002).
94. Stockinger B, Zal T, Zal A, Gray D. B cells solicit their own help from T cells. J. Exp. Med. 183(3), 891-899 (1996).
95. + T cells to produce IL-4. J. Immunol. 158(9), 4171-4179 (1997).
96. Skok J, Poudrier J, Gray D. Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development. J. Immunol. 163(8), 4284-4291(1999).
97. Harris DP, Haynes L, Sayles PC et al. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat. Immunol. 1(6),475-482 (2000).
98. Moulin V, Andris F, Thielemans K, Maliszewski C, Urbain J, Moser M. B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J. Exp. Med. 192(4), 475-482 (2000).
99. Segal BM, Dwyer BK, Shevach EM. An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. J. Exp. Med. 187(4), 537-546 (1998).
100. Jacobs LD, Cookfair DL, Rudick RA et al. Intramuscular interferon β la for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann. Neurol. 39(3), 285-294 (1996).
101. Wang X, Chen M, Wandinger KP, Williams G, Dhib-Jalbut S. IFN-β-1b inhibits IL-12 production in peripheral blood mononudear cells in an IL-10-dependent mechanism: relevance to IFN-β-1b therapeutic effects in multiple sclerosis. J. Immunol. 165(1), 548-557 (2000).
102. Tuohy VK, Yu M, Yin L, Mathisen PM, Johnson JM, Kawczak JA. Modulation of the IL-10/IL-12 cytokine circuit by interferon-β inhibits the development of epitope spreading and disease progression in murine autoimmune encephalomyelitis. J. Neuroimmunol. 111(1-2), 55-63 (2000).
103. + B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity 22(4), 467-477 (2005).
104. Bettelli E, Carrier Y, Gao W et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090), 235-238 (2006).
105. Cua DJ, Hutchins B, LaFace DM, Stohlman SA, Coffman RL. Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J. Immunol. 166(1), 602-608 (2001).
106. D'Amico G, Frascaroli G, Bianchi G et al. Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys. Nat. Immunol. 1(5), 387-391 (2000).
107. Cumberbatch M, Dearman RJ, Kimber I. Langerhans cells require signals from both tumour necrosis factor-α and interleukin-1 β for migration. Immunology 92(3), 388-395 (1997).
108. Strle K, Zhou JH, Shen WH et al. Interleukin-10 in the brain. Crit. Rev. Immunol. 21(5), 427-449 (2001).
109. MacPhee IA, Antoni FA, Mason DW. Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J. Exp. Med. 169 (2), 431-445 (1989).
110. Kumar V, Sercarz E. An integrative model of regulation centered on recognition of TCR peptide/MHC complexes. Immunol. Rev. 182, 113-421 (2001).
111. + regulatory cells within the central nervous system. J. Immunol. 175(5), 3025-3032 (2005).
112. Ponomarev ED, Dittel BN. γδ T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism. J. Immunol. 174(8), 4678-4687 (2005).
113. + T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J. Immunol. 178(6), 3447-3456(2007).
114. + T cell colitis through interaction with regulatory T cell subsets. Proc. Natl Acad. Sci. USA 102(6), 2010-2015 (2005).
115. Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat. Rev. Immunol. 3(11), 879-889 (2003).
116. D'Orazio TJ, Niederkorn JY. Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber-associated immune deviation (ACAID). Immunology 95(1), 47-55 (1998).
117. D'Orazio TJ, Mayhew E, Niederkorn JY. Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J. Immunol. 166(1), 26-32 (2001).
118. Hara Y, Okamoto S, Rouse B, Streilein JW. Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type. J Immunol. 151(10), 5162-5171 (1993).
119. Skelsey ME, Mayhew E, Niederkorn JY. Splenic B cells act as antigen presenting cells for the induction of anterior chamber-associated immune deviation. Invest. Ophthalmol. Vis. Sci. 44(12), 5242-5251 (2003).
120. Ashour HM, Niederkorn JY. Peripheral tolerance via the anterior chamber of the eye: role of B cells in MHC class I and II antigen presentation. J. Immunol. 176(10), 5950-5957(2006).
121. Lanzavecchia A. Antigen uptake and accumulation in antigen-specific B cells. Immunol. Rev. 99, 39-51 (1987).
122. Parish CR, Liew FY. Immune response to chemically modified flagellin. 3. Enhanced cell-mediated immunity during high and low zone antibody tolerance to flagellin. J. Exp. Med. 135(2), 298-311 (1972).
123. Finkelman FD, Snapper CM, Mountz JD, Katona IM. Polyclonal activation of the murine immune system by a goat antibody to mouse IgD. IX. Induction of a polyclonal IgE response. J. Immunol. 138(9), 2826-2830 (1987).
124. Macaulay AE, DeKruyff RH, Umetsu DT. Antigen-primed T cells from B cell-deficient JHD mice fail to provide B cell help. J. Immunol. 160 (4), 1694-1700 (1998).
125. Metlay JP, Pure E, Steinman RM. Distinct features of dendritic cells and anti-Ig activated B cells as stimulators of the primary mixed leukocyte reaction. J. Exp. Med. 169(1), 239-254 (1989).
126. Lassila O, Vainio O, Matzinger P. Can B cells turn on virgin T cells? Nature 334(6179), 253-255 (1988).
127. Eynon EE, Parker DC. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J. Exp. Med. 175(1), 131-138 (1992).
128. Day MJ, Tse AG, Puklavec M, Simmonds SJ, Mason DW. Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats. J. Exp. Med. 175(3), 655-659 (1992).
129. Saoudi A, Simmonds S, Huitinga I, Mason D. Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells. J. Exp. Med. 182(2), 335-344 (1995).
130. Chen C, Rivera A, Ron N, Dougherty JP, Ron Y. A gene therapy approach for treating T-cell-mediated autoimmune diseases. Blood 97(4), 886-894 (2001).
131. Chen CC, Rivera A, Dougherty JP, Ron Y. Complete protection from relapsing experimental autoimmune encephalomyelitis induced by syngeneic B cells expressing the autoantigen. Blood 103(12), 4616-4618 (2004).
132. Xu B, Scott DW. A novel retroviral gene therapy approach to inhibit specific antibody production and suppress experimental autoimmune encephalomyelitis induced by MOG and MBP. Clin. Immunol. 111(1), 47-52 (2004).
133. Soukhareva N, Jiang Y, Scott DW. Treatment of diabetes in NOD mice by gene transfer of Ig-fusion proteins into B cells: role of T regulatory cells. Cell. Immunol. 240(1), 41-46 (2006).
134. Primary immunodeficiency diseases. Report of a WHO scientific group. Clin. Exp. Immunol. 109(Suppl. 1), 1-28 (1997).
135. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin. Immunol. 92(1), 34-48 (1999).
136. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N. Engl. J. Med. 345(10), 747-755 (2001).
137. Blasczyk R, Westhoff U, Grosse-Wilde H. Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations. Lancet 341(8848), 789-790 (1993).
138. Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 349(9052), 589-593 (1997).
139. Achiron A, Gabbay U, Gilad R et al. Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses. Neurology 50(2), 398-402 (1998).
140. Achiron A, Kishner I, Sarova-Pinhas I et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch. Neurol. 61(10), 1515-1520 (2004).
141. Hommes OR, Sorensen PS, Fazekas F et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet 364(9440), 1149-1156(2004).
142. Reske D, Schoppe S, Broicher C, Petereit HF. The immunomodulatory properties of in vitro immunoglobulins are dose-dependent. Acta Neurol. Scand. 108(4), 267-273 (2003).
143. Aktas O, Waiczies S, Grieger U, Wendling U, Zschenderlein R, Zipp F. Polyspecific inummoglobulins (IVIg) suppress proliferation of human (auto)antigen-specific T cells without inducing apoptosis. J. Neuroimmunol. 114(1-2), 160-167 (2001).
144. Durelli L, Isoardo G. High-dose intravenous immunoglobulin treatment of multiple sclerosis. Neurol. Sci. 23(Suppl. 1), S39-S48 (2002).
145. Sorensen PS, Wanscher B, Jensen CV et al. Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 50(5), 1273-1281 (1998).
146. Jorgensen SH, Storm N, Jensen PE, Laursen H, Sorensen PS. IVIG enters the central nervous system during treatment of experimental autoimmune encephalomyelitis and is localised to inflammatory lesions. Exp. Brain Res. 178(4), 462-469 (2006).
147. Rossi F, Dietrich G, Kazatchkine MD. Anti-idiotypes against autoantibodies in normal immunoglobulins: evidence for network regulation of human autoimmune responses. Immunol. Rev. 110, 135-149 (1989).
148. Stangel M, Compston A, Scolding NJ. Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins ("IVIg"). J. Neuroimmunol. 103(2), 195-201 (2000).
149. Janke AD, Giuliani F, Yong VW. IVIg attenuates T cell-mediated killing of human neurons. J. Neuroimmunol. 177(1-2), 181-188 (2006).
150. Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions. Ann. Neurol. 33(2), 137-151 (1993).
151. Rodriguez M, Lennon VA, Benveniste EN, Merrill JE. Remyelination by oligodendrocytes stimulated by antiserum. to spinal cord. J. Neuropathol. Exp. Neurol. 46(1), 84-95 (1987).
152. Rodriguez M, Lennon VA. Immunoglobulins promote remyelination in the central nervous system. Ann. Neurol. 27(1),12-17 (1990).
153. Asakura K, Miller DJ, Pease LR, Rodriguez M. Targeting Of IgMκ antibodies to oligodendrocytes promotes CNS remyelination. J. Neurosci. 18(19), 7700-7708(1998).
154. Bieber AJ, Warrington A, Pease LR, Rodriguez M. Humoral autoimmunity as a mediator of CNS repair. Trends Neurosci. 24(11 Suppl.), S39-S44 (2001).
155. Barisal R, Pfeiffer SE. Reversible inhibition of oligodendrocyte progenitor differentiation by a monoclonal antibody against surface galactolipids. Proc. Natl Acad Sci. USA 86(16), 6181-6185 (1989).
156. Rosenbluth J, Liu Z, Guo D, Schiff R. Inhibition of CNS myelin development in vivo by implantation of anti-GalC hybridoma cells. J. Neurocytol. 23 (11), 699-707(1994).
157. Nakahara J, Tan-Takeuchi K, Seiwa C et al. Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation. Dev. Cell 4(6), 841-852 (2003).
158. Keirstead HS, Blakemore WF. Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord. J. Neuropathol. Exp. Neurol. 56(11),1191-1201 (1997).
159. Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346(3), 165-173 (2002).