Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients

Journal of Neuroimmunology

Volumn 261, Issue 1-2, 2013, Pages 98-107

  Fraussen, Judith ^a   Vrolix, Kathleen ^b   Claes, Nele ^a   Martinez Martinez, Pilar ^b   Losen, Mario ^b   Hupperts, Raymond ^b,c   Van Wijmeersch, Bart ^a,d,e   Espiño, Mercedes ^f   Villar, Luisa M ^f   De Baets, Marc H ^a,b   Stinissen, Piet ^a   Somers, Veerle ^a  

^a HASSELT UNIVERSITY   (Belgium)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c Zuyderland Medical Centre   (Netherlands)

^d PHL University College   (Belgium)

^e Revalidatie and MS Centrum   (Belgium)

^f HOSPITAL RAMÓN Y CAJAL   (Spain)

Author keywords

Autoreactivity; B cell immortalization; Clinically isolated syndrome; Clonal B cell expansion; Complementarity determining region 3; Multiple sclerosis

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; B LYMPHOCYTE RECEPTOR; PHOSPHATIDYLCHOLINE;

ADULT; ANTIBODY PRODUCTION; ANTIGEN BINDING; ARTICLE; B LYMPHOCYTE; CELL IMMORTALIZATION; CLINICAL ARTICLE; CONTROLLED STUDY; DEMYELINATING DISEASE; FEMALE; GENE MUTATION; HUMAN; HUMAN CELL; IMMUNOGLOBULIN HEAVY CHAIN GENE; LYMPHOCYTE CLONE; MALE; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; SEQUENCE ANALYSIS;

AUTOREACTIVITY; B CELL IMMORTALIZATION; CLINICALLY ISOLATED SYNDROME; CLONAL B CELL EXPANSION; COMPLEMENTARITY DETERMINING REGION 3; MULTIPLE SCLEROSIS;

ADOLESCENT; ADULT; AUTOANTIBODIES; AUTOANTIGENS; B-LYMPHOCYTES; CELL LINE, TRANSFORMED; CLONAL SELECTION, ANTIGEN-MEDIATED; FEMALE; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MIDDLE AGED; MULTIPLE SCLEROSIS;

EID: 84880774149     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2013.05.002     Document Type: Article

References (72)

1. Adderson E.E., Shackelford P.G., Quinn A., Wilson P.M., Cunningham M.W., Insel R.A., Carroll W.L. Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens. J. Clin. Invest. 1993, 91(6):2734-2743.
2. Archelos J.J., Storch M.K., Hartung H.P. The role of B cells and autoantibodies in multiple sclerosis. Ann. Neurol. 2000, 47(6):694-706.
3. Baranzini S.E., Jeong M.C., Butunoi C., Murray R.S., Bernard C.C., Oksenberg J.R. B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions. J. Immunol. 1999, 163(9):5133-5144.
4. Bar-Or A., Calabresi P.A., Arnold D., Markowitz C., Shafer S., Kasper L.H., Waubant E., Gazda S., Fox R.J., Panzara M., Sarkar N., Agarwal S., Smith C.H. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann. Neurol. 2008, 63(3):395-400.
5. Bennett J.L., Haubold K., Ritchie A.M., Edwards S.J., Burgoon M., Shearer A.J., Gilden D.H., Owens G.P. CSF IgG heavy-chain bias in patients at the time of a clinically isolated syndrome. J. Neuroimmunol. 2008, 199(1-2):126-132.
6. Brezinschek H.P., Brezinschek R.I., Lipsky P.E. Analysis of the heavy chain repertoire of human peripheral B cells using single-cell polymerase chain reaction. J. Immunol. 1995, 155(1):190-202.
7. Broman T. Blood-brain barrier damage in multiple sclerosis supravital test-observations. Acta Neurol. Scand. 1964, (Suppl. 40). (Suppl.-4).
8. Charles E.D., Green R.M., Marukian S., Talal A.H., Lake-Bakaar G.V., Jacobson I.M., Rice C.M., Dustin L.B. Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia. Blood 2008, 111(3):1344-1356.
9. Cole S.R., Beck R.W., Moke P.S., Kaufman D.I., Tourtellotte W.W. The predictive value of CSF oligoclonal banding for MS 5years after optic neuritis. Optic Neuritis Study Group. Neurology 1998, 51(3):885-887.
10. Colombo M., Dono M., Gazzola P., Roncella S., Valetto A., Chiorazzi N., Mancardi G.L., Ferrarini M. Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients. J. Immunol. 2000, 164(5):2782-2789.
11. Colombo M., Dono M., Gazzola P., Chiorazzi N., Mancardi G., Ferrarini M. Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients. Eur. J. Immunol. 2003, 33(12):3433-3438.
12. Cook G.P., Tomlinson I.M. The human immunoglobulin VH repertoire. Immunol. Today 1995, 16(5):237-242.
13. Cross A.H., Trotter J.L., Lyons J. B cells and antibodies in CNS demyelinating disease. J. Neuroimmunol. 2001, 112(1-2):1-14.
14. Ebers G.C., Vinuela F.V., Feasby T., Bass B. Multifocal CT enhancement in MS. Neurology 1984, 34(3):341-346.
15. Esiri M.M. Immunoglobulin-containing cells in multiple-sclerosis plaques. Lancet 1977, 2(8036):478.
16. Ferraro D., Simone A.M., Bedin R., Galli V., Vitetta F., Federzoni L., D'Amico R., Merelli E., Nichelli P.F., Sola P. Cerebrospinal fluid oligoclonal IgM bands predict early conversion to clinically definite multiple sclerosis in patients with Clinically Isolated Syndrome. J. Neuroimmunol. 2013, 257(1-2):76-81.
17. Filippi M., Rocca M.A., Martino G., Horsfield M.A., Comi G. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann. Neurol. 1998, 43(6):809-814.
18. Fisniku L.K., Brex P.A., Altmann D.R., Miszkiel K.A., Benton C.E., Lanyon R., Thompson A.J., Miller D.H. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008, 131(Pt. 3):808-817.
19. Fraussen J., Vrolix K., Martinez-Martinez P., Losen M., De Baets M.H., Stinissen P., Somers V. B cell characterization and reactivity analysis in multiple sclerosis. Autoimmun. Rev. 2009, 8(8):654-658.
20. Fraussen J., Vrolix K., Martinez-Martinez P., Losen M., Meulemans E., De Baets M.H., Stinissen P., Somers V. A novel method for making human monoclonal antibodies. J. Autoimmun. 2010, 35(2):130-134.
21. Genain C.P., Cannella B., Hauser S.L., Raine C.S. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. 1999, 5(2):170-175.
22. 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. 1994, 49(1-2):153-159.
23. Graus Y., Meng F., Vincent A., van B.V., De Baets M. Sequence analysis of anti-AChR antibodies in experimental autoimmune myasthenia gravis. J. Immunol. 1995, 154(12):6382-6396.
24. Graus Y.F., De Baets M.H., Parren P.W., Berrih-Aknin S., Wokke J., Breda Vriesman P.J., Burton D.R. Human anti-nicotinic acetylcholine receptor recombinant Fab fragments isolated from thymus-derived phage display libraries from myasthenia gravis patients reflect predominant specificities in serum and block the action of pathogenic serum antibodies. J. Immunol. 1997, 158(4):1919-1929.
25. Hafler D.A. Multiple sclerosis. J. Clin. Invest. 2004, 113(6):788-794.
26. Harp C., Lee J., Lambracht-Washington D., Cameron E., Olsen G., Frohman E., Racke M., Monson N. Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection. J. Neuroimmunol. 2007, 183(1-2):189-199.
27. Hauser S.L., Waubant E., Arnold D.L., Vollmer T., Antel J., Fox R.J., Bar-Or A., Panzara M., Sarkar N., Agarwal S., Langer-Gould A., Smith C.H. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 2008, 358(7):676-688.
28. Hemmer B., Archelos J.J., Hartung H.P. New concepts in the immunopathogenesis of multiple sclerosis. Nat. Rev. Neurosci. 2002, 3(4):291-301.
29. Kabat E.A., Glusman M., Knaub V. Quantitative estimation of the albumin and gamma-globulin in normal and pathological cerebrospinal fluid by immunochemical methods. Am. J. Med. 1948, 4:653-662.
30. Kermode A.G., Thompson A.J., Tofts P., MacManus D.G., Kendall B.E., Kingsley D.P., Moseley I.F., Rudge P., McDonald W.I. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 1990, 113(Pt. 5):1477-1489.
31. Krumbholz M., Theil D., Derfuss T., Rosenwald A., Schrader F., Monoranu C.M., Kalled S.L., Hess D.M., Serafini B., Aloisi F., Wekerle H., Hohlfeld R., Meinl E. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J. Exp. Med. 2005, 201(2):195-200.
32. Kwon E.E., Prineas J.W. Blood-brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study. J. Neuropathol. Exp. Neurol. 1994, 53(6):625-636.
33. Lanzavecchia A. Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu. Rev. Immunol. 1990, 8:773-793.
34. Lee-Chang C., Zephir H., Top I., Dubucquoi S., Trauet J., Prin L., Vermersch P. B-cell subsets up-regulate alpha4 integrin and accumulate in the cerebrospinal fluid in clinically isolated syndrome suggestive of multiple sclerosis onset. Neurosci. Lett. 2011, 487(3):273-277.
35. 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):707-717.
36. Luo J., Taylor P., Losen M., De Baets M.H., Shelton G.D., Lindstrom J. Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity. J. Neurosci. 2009, 29(44):13898-13908.
37. Magraner M.J., Bosca I., Simo-Castello M., Garcia-Marti G., Alberich-Bayarri A., Coret F., Alvarez-Cermeno J.C., Marti-Bonmati L., Villar L.M., Casanova B. Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes. Neuroradiology 2012, 54(1):5-12.
38. Malynn B.A., Yancopoulos G.D., Barth J.E., Bona C.A., Alt F.W. Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice. J. Exp. Med. 1990, 171(3):843-859.
39. Marchi N., Cavaglia M., Fazio V., Bhudia S., Hallene K., Janigro D. Peripheral markers of blood-brain barrier damage. Clin. Chim. Acta 2004, 342(1-2):1-12.
40. McDonald W.I., Compston A., Edan G., Goodkin D., Hartung H.P., Lublin F.D., McFarland H.F., Paty D.W., Polman C.H., Reingold S.C., Sandberg-Wollheim M., Sibley W., Thompson A., van den N.S., Weinshenker B.Y., Wolinsky J.S. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 2001, 50(1):121-127.
41. Miller D., Barkhof F., Montalban X., Thompson A., Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol. 2005, 4(5):281-288.
42. Monson N.L., Brezinschek H.P., Brezinschek R.I., Mobley A., Vaughan G.K., Frohman E.M., Racke M.K., Lipsky P.E. Receptor revision and atypical mutational characteristics in clonally expanded B cells from the cerebrospinal fluid of recently diagnosed multiple sclerosis patients. J. Neuroimmunol. 2005, 158(1-2):170-181.
43. Naismith R.T., Piccio L., Lyons J.A., Lauber J., Tutlam N.T., Parks B.J., Trinkaus K., Song S.K., Cross A.H. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 2010, 74(23):1860-1867.
44. Owens G.P., Kraus H., Burgoon M.P., Smith-Jensen T., Devlin M.E., Gilden D.H. Restricted use of VH4 germline segments in an acute multiple sclerosis brain. Ann. Neurol. 1998, 43(2):236-243.
45. Owens G.P., Ritchie A.M., Burgoon M.P., Williamson R.A., Corboy J.R., Gilden D.H. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J. Immunol. 2003, 171(5):2725-2733.
46. Owens G.P., Winges K.M., Ritchie A.M., Edwards S., Burgoon M.P., Lehnhoff L., Nielsen K., Corboy J., Gilden D.H., Bennett J.L. VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis. J. Immunol. 2007, 179(9):6343-6351.
47. Peferoen L.A., Lamers F., Lodder L.N., Gerritsen W.H., Huitinga I., Melief J., Giovannoni G., Meier U., Hintzen R.Q., Verjans G.M., van Nierop G.P., Vos W., Peferoen-Baert R.M., Middeldorp J.M., van der Valk P., Amor S. Epstein Barr virus is not a characteristic feature in the central nervous system in established multiple sclerosis. Brain 2010, 133(Pt. 5):e137.
48. Polman C.H., Reingold S.C., Banwell B., Clanet M., Cohen J.A., Filippi M., Fujihara K., Havrdova E., Hutchinson M., Kappos L., Lublin F.D., Montalban X., O'Connor P., Sandberg-Wollheim M., Thompson A.J., Waubant E., Weinshenker B., Wolinsky J.S. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 2011, 69(2):292-302.
49. 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(5):1045-1050.
50. Qin Y., Duquette P., Zhang Y., Olek M., Da R.R., Richardson J., Antel J.P., Talbot P., Cashman N.R., Tourtellotte W.W., Wekerle H., van den N.S. 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):1081-1088.
51. Ritchie A.M., Gilden D.H., Williamson R.A., Burgoon M.P., Yu X., Helm K., Corboy J.R., Owens G.P. Comparative analysis of the CD19+ and CD138+ cell antibody repertoires in the cerebrospinal fluid of patients with multiple sclerosis. J. Immunol. 2004, 173(1):649-656.
52. Rock K.L., Benacerraf B., Abbas A.K. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J. Exp. Med. 1984, 160(4):1102-1113.
53. Sargsyan S.A., Shearer A.J., Ritchie A.M., Burgoon M.P., Anderson S., Hemmer B., Stadelmann C., Gattenlohner S., Owens G.P., Gilden D., Bennett J.L. Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis. Neurology 2010, 74(14):1127-1135.
54. 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(2):164-174.
55. Serafini B., Rosicarelli B., Franciotta D., Magliozzi R., Reynolds R., Cinque P., Andreoni L., Trivedi P., Salvetti M., Faggioni A., Aloisi F. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J. Exp. Med. 2007, 204(12):2899-2912.
56. Smith-Jensen T., Burgoon M.P., Anthony J., Kraus H., Gilden D.H., Owens G.P. Comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains reveals an antigen-driven response. Neurology 2000, 54(6):1227-1232.
57. Soon D., Tozer D.J., Altmann D.R., Tofts P.S., Miller D.H. Quantification of subtle blood-brain barrier disruption in non-enhancing lesions in multiple sclerosis: a study of disease and lesion subtypes. Mult. Scler. 2007, 13(7):884-894.
58. Souto-Carneiro M.M., Longo N.S., Russ D.E., Sun H.W., Lipsky P.E. Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly developed software algorithm, JOINSOLVER. J. Immunol. 2004, 172(11):6790-6802.
59. Stuve O., Leussink V.I., Frohlich R., Hemmer B., Hartung H.P., Menge T., Kieseier B.C. Long-term B-lymphocyte depletion with rituximab in patients with relapsing-remitting multiple sclerosis. Arch. Neurol. 2009, 66(2):259-261.
60. Thangarajh M., Gomez-Rial J., Hedstrom A.K., Hillert J., Alvarez-Cermeno J.C., Masterman T., Villar L.M. Lipid-specific immunoglobulin M in CSF predicts adverse long-term outcome in multiple sclerosis. Mult. Scler. 2008, 14(9):1208-1213.
61. van der Neut K.M., Schuurman J., Losen M., Bleeker W.K., Martinez-Martinez P., Vermeulen E., den Bleker T.H., Wiegman L., Vink T., Aarden L.A., De Baets M.H., van de Winkel J.G., Aalberse R.C., Parren P.W. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 2007, 317(5844):1554-1557.
62. van Dongen J.J., Langerak A.W., Bruggemann M., Evans P.A., Hummel M., Lavender F.L., Delabesse E., Davi F., Schuuring E., Garcia-Sanz R., van Krieken J.H., Droese J., Gonzalez D., Bastard C., White H.E., Spaargaren M., Gonzalez M., Parreira A., Smith J.L., Morgan G.J., Kneba M., Macintyre E.A. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003, 17(12):2257-2317.
63. Venken K., Hellings N., Thewissen M., Somers V., Hensen K., Rummens J.L., Medaer R., Hupperts R., Stinissen P. Compromised CD4+ CD25 (high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology 2008, 123(1):79-89.
64. Villar L.M., Gonzalez-Porque P., Masjuan J., Alvarez-Cermeno J.C., Bootello A., Keir G. A sensitive and reproducible method for the detection of oligoclonal IgM bands. J. Immunol. Methods 2001, 258(1-2):151-155.
65. Villar L.M., Sadaba M.C., Roldan E., Masjuan J., Gonzalez-Porque P., Villarrubia N., Espino M., Garcia-Trujillo J.A., Bootello A., Alvarez-Cermeno J.C. Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J. Clin. Invest. 2005, 115(1):187-194.
66. von Budingen H.C., Kuo T.C., Sirota M., van Belle C.J., Apeltsin L., Glanville J., Cree B.A., Gourraud P.A., Schwartzburg A., Huerta G., Telman D., Sundar P.D., Casey T., Cox D.R., Hauser S.L. B cell exchange across the blood-brain barrier in multiple sclerosis. J. Clin. Invest. 2012, 122(12):4533-4543.
67. Vrolix K., Fraussen J., Molenaar P.C., Losen M., Somers V., Stinissen P., De Baets M.H., Martinez-Martinez P. The auto-antigen repertoire in myasthenia gravis. Autoimmunity 2010, 43(5-6):380-400.
68. Widhopf G.F., Rassenti L.Z., Toy T.L., Gribben J.G., Wierda W.G., Kipps T.J. Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood 2004, 104(8):2499-2504.
69. Willis S.N., Stadelmann C., Rodig S.J., Caron T., Gattenloehner S., Mallozzi S.S., Roughan J.E., Almendinger S.E., Blewett M.M., Bruck W., Hafler D.A., O'Connor K.C. Epstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 2009, 132(Pt. 12):3318-3328.
70. Yamada M., Wasserman R., Reichard B.A., Shane S., Caton A.J., Rovera G. Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J. Exp. Med. 1991, 173(2):395-407.
71. Yancopoulos G.D., Desiderio S.V., Paskind M., Kearney J.F., Baltimore D., Alt F.W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature 1984, 311(5988):727-733.
72. Ziemssen T., Ziemssen F. The role of the humoral immune system in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Autoimmun. Rev. 2005, 4(7):460-467.