B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells

Journal of Experimental Medicine

Volumn 209, Issue 5, 2012, Pages 1001-1010

  Barr, Tom A ^a   Shen, Ping ^b   Brown, Sheila ^a   Lampropoulou, Vicky ^b   Roch, Toralf ^b   Lawrie, Sarah ^c   Fan, Boli ^c   O'Connor, Richard A ^a   Anderton, Stephen M ^a   Bar Or, Amit ^c   Fillatreau, Simon ^b   Gray, David ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b DEUTSCHES RHEUMA FORSCHUNGSZENTRUM   (Germany)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; RITUXIMAB; MONOCLONAL ANTIBODY; PRIMER DNA;

ADULT; AGED; ALLERGIC ENCEPHALOMYELITIS; ARTICLE; AUTOIMMUNITY; B CELL DEPLETION THERAPY; B CELL RECONSTITUTION; B LYMPHOCYTE; CELLULAR IMMUNITY; CENTRAL NERVOUS SYSTEM; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE COURSE; DISEASE SEVERITY; FEMALE; HUMAN; HUMAN CELL; HUMORAL IMMUNITY; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; MALE; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; T LYMPHOCYTE ACTIVATION; WILD TYPE; ADOPTIVE TRANSFER; ANALYSIS OF VARIANCE; ANIMAL; DRUG EFFECT; FLOW CYTOMETRY; GENETICS; GERMFREE ANIMAL; IMMUNOLOGY; LYMPHOCYTE DEPLETION; METHODOLOGY; MOUSE; NONPARAMETRIC TEST; PATHOPHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SECRETION;

ADOPTIVE TRANSFER; ANALYSIS OF VARIANCE; ANIMALS; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; B-LYMPHOCYTES; DNA PRIMERS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FLOW CYTOMETRY; HUMANS; INTERLEUKIN-6; LYMPHOCYTE DEPLETION; MICE; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SPECIFIC PATHOGEN-FREE ORGANISMS; STATISTICS, NONPARAMETRIC;

EID: 84863803849     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20111675     Document Type: Article

References (50)

1. Anderton, S.M., and S. Fillatreau. 2008. Activated B cells in autoimmune diseases: the case for a regulatory role. Nat. Clin. Pract. Rheumatol. 4: 657-666. http://dx.doi.org/10.1038/ncprheum0950
2. Balázs, M., F. Martin, T. Zhou, and J. Kearney. 2002. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity. 17:341-352. http://dx.doi.org/10.1016/ S1074-7613(02)00389-8
3. Bar-Or, A., P.A. Calabresi, D. Arnold, C. Markowitz, S. Shafer, L.H. Kasper, E. Waubant, S. Gazda, R.J. Fox, M. Panzara, et al. 2008. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann. Neurol. 63:395-400. http://dx.doi.org/10.1002/ana.21363
4. Bar-Or, A., L. Fawaz, B. Fan, P.J. Darlington, A. Rieger, C. Ghorayeb, P.A. Calabresi, E. Waubant, S.L. Hauser, J. Zhang, and C.H. Smith. 2010. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann. Neurol. 67:452-461. http://dx.doi.org/10.1002/ana.21939
5. Barr, T.A., S. Brown, G. Ryan, J. Zhao, and D. Gray. 2007. TLRmediated stimulation of APC: Distinct cytokine responses of B cells and dendritic cells. Eur. J. Immunol. 37:3040-3053. http://dx.doi.org/10.1002/eji.200636483
6. Barr, T.A., S. Brown, P. Mastroeni, and D. Gray. 2010. TLR and B cell receptor signals to B cells differentially program primary and memory Th1 responses to Salmonella enterica. J. Immunol. 185:2783-2789. http:// dx.doi.org/10.4049/jimmunol.1001431
7. Belnoue, E., M. Pihlgren, T.L. McGaha, C. Tougne, A.F. Rochat, C. Bossen, P. Schneider, B. Huard, P.H. Lambert, and C.A. Siegrist. 2008. APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood. 111:2755- 2764. http://dx.doi.org/10.1182/blood-2007-09-110858
8. Bettelli, E., Y. Carrier, W. Gao, T. Korn, T.B. Strom, M. Oukka, H.L. Weiner, and V.K. Kuchroo. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 441:235-238. http://dx.doi.org/10.1038/nature04753
9. Blair, P.A., L.Y. Noreña, F. Flores-Borja, D.J. Rawlings, D.A. Isenberg, M.R. Ehrenstein, and C. Mauri. 2010. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 32:129-140. http://dx.doi.org/10.1016/j.immuni.2009.11.009
10. Bouaziz, J.D., S. Calbo, M. Maho-Vaillant, A. Saussine, M. Bagot, A. Bensussan, and P. Musette. 2010. IL-10 produced by activated human B cells regulates CD4(+) T-cell activation in vitro. Eur. J. Immunol. 40:2686-2691. http://dx.doi.org/10.1002/eji.201040673
11. Burdin, N., C. Van Kooten, L. Galibert, J.S. Abrams, J. Wijdenes, J. Banchereau, and F. Rousset. 1995. Endogenous IL-6 and IL-10 contribute to the differentiation of CD40-activated human B lymphocytes. J. Immunol. 154:2533-2544.
12. Cognasse, F., H. Hamzeh-Cognasse, S. Lafarge, P. Chavarin, B. Pozzetto, Y. Richard, and O. Garraud. 2008. Identification of two subpopulations of purified human blood B cells, CD27- CD23+ and CD27high CD80+, that strongly express cell surface Toll-like receptor 9 and secrete high levels of interleukin-6. Immunology. 125:430-437. http://dx.doi.org/10.1111/j.1365-2567.2008.02844.x
13. Cross, A.H., J.L. Stark, J. Lauber, M.J. Ramsbottom, and J.A. Lyons. 2006. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J. Neuroimmunol. 180:63-70. http://dx.doi.org/ 10.1016/j.jneuroim.2006.06.029
14. Duddy, M., M. Niino, F. Adatia, S. Hebert, M. Freedman, H. Atkins, H.J. Kim, and A. Bar-Or. 2007. Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J. Immunol. 178:6092-6099.
15. Edwards, J.C., and G. Cambridge. 2006. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat. Rev. Immunol. 6:394-403. http://dx.doi.org/10.1038/nri1838
16. Eugster, H.P., K. Frei, M. Kopf, H. Lassmann, and A. Fontana. 1998. IL-6-deficient mice resist myelin oligodendrocyte glycoproteininduced autoimmune encephalomyelitis. Eur. J. Immunol. 28:2178-2187. http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2178::AID-IMMU2178>3.0.CO;2-D
17. Fillatreau, S., and S.M. Anderton. 2007. B-cell function in CNS inflammatory demyelinating disease: a complexity of roles and a wealth of possibilities. Expert Rev. Clin. Immunol. 3:565-578. http://dx.doi.org/10.1586/ 1744666X.3.4.565
18. Fillatreau, S., C.H. Sweenie, M.J. McGeachy, D. Gray, and S.M. Anderton. 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3:944-950. http://dx.doi.org/10.1038/ni833
19. Fillatreau, S., D. Gray, and S.M. Anderton. 2008. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat. Rev. Immunol. 8:391-397. http://dx.doi.org/10.1038/nri2315
20. Good, K.L., V.L. Bryant, and S.G. Tangye. 2006. Kinetics of human B cell behavior and amplification of proliferative responses following stimulation with IL-21. J. Immunol. 177:5236-5247.
21. Gray, D., and M. Gray. 2010. What are regulatory B cells? Eur. J. Immunol. 40:2677-2679. http://dx.doi.org/10.1002/eji.201040961
22. Haak, S., A.L. Croxford, K. Kreymborg, F.L. Heppner, S. Pouly, B. Becher, and A. Waisman. 2009. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J. Clin. Invest. 119:61-69.
23. Hartung, H.P., and B.C. Kieseier. 2010. Atacicept: targeting B cells in multiple sclerosis. Ther. Adv. Neurol. Disord. 3:205-216. http://dx.doi.org/10.1177/1756285610371146
24. Hauser, S.L., E. Waubant, D.L. Arnold, T. Vollmer, J. Antel, R.J. Fox, A. Bar-Or, M. Panzara, N. Sarkar, S. Agarwal, et al; HERMES Trial Group. 2008. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 358:676-688. http://dx.doi.org/10.1056/NEJMoa0706383
25. Kala, M., S.N. Rhodes, W.H. Piao, F.D. Shi, D.I. Campagnolo, and T.L. Vollmer. 2010. B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis. Exp. Neurol. 221:136-145. http://dx.doi.org/10.1016/j.expneurol.2009.10.015
26. Komiyama, Y., S. Nakae, T. Matsuki, A. Nambu, H. Ishigame, S. Kakuta, K. Sudo, and Y. Iwakura. 2006. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 177:566-573.
27. Korn, T., E. Bettelli, M. Oukka, and V.K. Kuchroo. 2009. IL-17 and Th17 Cells. Annu. Rev. Immunol. 27:485-517. http://dx.doi.org/10.1146/ annurev.immunol.021908.132710
28. Kroenke, M.A., T.J. Carlson, A.V. Andjelkovic, and B.M. Segal. 2008. IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J. Exp. Med. 205:1535-1541. http://dx.doi.org/10.1084/jem.20080159
29. Lampropoulou, V., K. Hoehlig, T. Roch, P. Neves, E. Calderón Gómez, C.H. Sweenie, Y. Hao, A.A. Freitas, U. Steinhoff, S.M. Anderton, and S. Fillatreau. 2008. TLR-activated B cells suppress T cell-mediated autoimmunity. J. Immunol. 180:4763-4773.
30. Lampropoulou, V., E. Calderon-Gomez, T. Roch, P. Neves, P. Shen, U. Stervbo, P. Boudinot, S.M. Anderton, and S. Fillatreau. 2010. Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity. Immunol. Rev. 233:146-161. http://dx.doi.org/10.1111/j.0105-2896.2009.00855.x
31. Mann, M.K., K. Maresz, L.P. Shriver, Y. Tan, and B.N. Dittel. 2007. B cell regulation of CD4+CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J. Immunol. 178:3447-3456.
32. Martin, F., and A.C. Chan. 2006. B cell immunobiology in disease: evolving concepts from the clinic. Annu. Rev. Immunol. 24:467-496. http:// dx.doi.org/10.1146/annurev.immunol.24.021605.090517
33. Matsushita, T., K. Yanaba, J.D. Bouaziz, M. Fujimoto, and T.F. Tedder. 2008. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J. Clin. Invest. 118:3420-3430.
34. Mauri, C., D. Gray, N. Mushtaq, and M. Londei. 2003. Prevention of arthritis by interleukin 10-producing B cells. J. Exp. Med. 197:489-501. http://dx.doi.org/10.1084/jem.20021293
35. Mendel, I., A. Katz, N. Kozak, A. Ben-Nun, and M. Revel. 1998. Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice. Eur. J. Immunol. 28:1727-1737. http://dx.doi.org/10.1002/(SICI)1521-4141(199805)28:05<1727::AID-IMMU1727>3.0.CO;2-
36. Neurath, M.F., and S. Finotto. 2011. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 22:83-89. http://dx.doi.org/10.1016/j.cytogfr.2011.02.003
37. Neves, P., V. Lampropoulou, E. Calderon-Gomez, T. Roch, U. Stervbo, P. Shen, A.A. Kühl, C. Loddenkemper, M. Haury, S.A. Nedospasov, et al. 2010. Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection. Immunity. 33:777-790. http://dx.doi.org/10.1016/j.immuni.2010.10.016
38. O'Connor, B.P., V.S. Raman, L.D. Erickson, W.J. Cook, L.K. Weaver, C. Ahonen, L.L. Lin, G.T. Mantchev, R.J. Bram, and R.J. Noelle. 2004. BCMA is essential for the survival of long-lived bone marrow plasma cells. J. Exp. Med. 199:91-98. http://dx.doi.org/10.1084/jem.20031330
39. O'Connor, R.A., C.T. Prendergast, C.A. Sabatos, C.W. Lau, M.D. Leech, D.C. Wraith, and S.M. Anderton. 2008. Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis. J. Immunol. 181:3750-3754.
40. Oksenberg, J.R., S.E. Baranzini, S. Sawcer, and S.L. Hauser. 2008. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat. Rev. Genet. 9:516-526. http://dx.doi.org/10.1038/nrg2395
41. Okuda, Y., S. Sakoda, C.C. Bernard, H. Fujimura, Y. Saeki, T. Kishimoto, and T. Yanagihara. 1998. IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int. Immunol. 10:703-708. http://dx.doi.org/10.1093/intimm/10.5.703
42. Owens, G.P., J.L. Bennett, H. Lassmann, K.C. O'Connor, A.M. Ritchie, A. Shearer, C. Lam, X. Yu, M. Birlea, C. DuPree, et al. 2009. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Ann. Neurol. 65:639-649. http://dx.doi.org/ 10.1002/ana.21641
43. Pasare, C., and R. Medzhitov. 2003. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 299:1033-1036. http://dx.doi.org/10.1126/science.1078231
44. Ramgolam, V.S., Y. Sha, K.L. Marcus, N. Choudhary, L. Troiani, M. Chopra, and S. Markovic-Plese. 2011. B cells as a therapeutic target for IFN-? in relapsing-remitting multiple sclerosis. J. Immunol. 186:4518- 4526. http://dx.doi.org/10.4049/jimmunol.1000271
45. Samoilova, E.B., J.L. Horton, B. Hilliard, T.S. Liu, and Y. Chen. 1998. IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J. Immunol. 161:6480-6486.
46. Serada, S., M. Fujimoto, M. Mihara, N. Koike, Y. Ohsugi, S. Nomura, H. Yoshida, T. Nishikawa, F. Terabe, T. Ohkawara, et al. 2008. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 105:9041-9046. http://dx.doi.org/10.1073/pnas.0802218105
47. Wekerle, H. 1999. Remembering MOG: autoantibody mediated demyelination in multiple sclerosis? Nat. Med. 5:153-154. http://dx.doi.org/10.1038/5514
48. Yanaba, K., J.D. Bouaziz, K.M. Haas, J.C. Poe, M. Fujimoto, and T.F. Tedder. 2008. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 28:639-650. http://dx.doi.org/10.1016/j.immuni.2008.03.017
49. Zepp, J., L. Wu, and X. Li. 2011. IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol. 32:232- 239. http://dx.doi.org/10.1016/j.it.2011.02.007
50. Zhou, D., R. Srivastava, S. Nessler, V. Grummel, N. Sommer, W. Brück, H.P. Hartung, C. Stadelmann, and B. Hemmer. 2006. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc. Natl. Acad. Sci. USA. 103:19057- 19062. http://dx.doi.org/10.1073/pnas.0607242103