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B-Cell Depletion and Repopulation in Autoimmune Diseases

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Abstract

Although T-lymphocytes have long been regarded as the prime effector of autoimmune diseases, numerous studies have since highlighted a key role for B-lymphocytes. For example, disturbances in the distribution of circulating B-cell subsets were reported in primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE). Consequently, this was the rationale to treat such patients for B-cell depletion with anti-CD20 monoclonal antibody (rituximab). The aim of this review is to describe and analyze the B-cell subset distribution at baseline and after rituximab therapy in patients with SLE, rheumatoid arthritis, and pSS. Finally, we will compare factors that may interfere with anti-CD20-mediated B-cell depletion in these autoimmune diseases.

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References

  1. Youinou P, Daridon C, Steinfeld S, Pers JO (2007) A case for B cells in the pathogenesis of Sjögren’s syndrome. Trends Immunol (in press)

  2. Youinou P, Daridon C, Saraux A, Devauchelle V, Pers JO (2006) Is B-cell the conductor of the lymphocyte orchestra in the salivary glands of patients with primary Sjögren’s syndrome. Clin Exp Rheumatol 24:491–492

    PubMed  CAS  Google Scholar 

  3. Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R (1997) IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90:2188–2195

    PubMed  CAS  Google Scholar 

  4. Leandro MJ, Edwards JC, Cambridge G, Ehrenstein MR, Isenberg DA (2002) An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum 46:2673–2677

    Article  PubMed  Google Scholar 

  5. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581

    Article  PubMed  CAS  Google Scholar 

  6. Pijpe J, van Imhoff GW, Spijkervet FK, Roodenburg JL, Wolbink GJ, Mansour K, Vissink A, Kallenberg CG, Bootsma H (2005) Rituximab treatment in patients with primary Sjögren’s syndrome: an open-label phase II study. Arthritis Rheum 52:2740–2750

    Article  PubMed  CAS  Google Scholar 

  7. Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Quintin-Roué I, Cochener B, Youinou P, Saraux A (2007) Improvement of Sjögren’s syndrome after two infusions of rituximab (anti-CD20). Arthritis Care Res 57(2):310–317

    Article  CAS  Google Scholar 

  8. Edwards JC, Cambridge G (2006) B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 6:394–403

    Article  PubMed  CAS  Google Scholar 

  9. Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC (2006) Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 54:613–620

    Article  PubMed  CAS  Google Scholar 

  10. Roll P, Palanichamy A, Kneitz C, Dorner T, Tony HP (2006) Regeneration of B cell subsets after transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Arthritis Rheum 54:2377–2386

    Article  PubMed  CAS  Google Scholar 

  11. Anolik JH, Barnard J, Cappione A, Pugh-Bernard AE, Felgar RE, Looney RJ, Sanz I (2004) Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum 50:3580–3590

    Article  PubMed  CAS  Google Scholar 

  12. Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, Berthou C, Saraux A, Youinou P (2007) BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren’s syndrome. Arthritis Rheum 56:1464-1477

    Article  Google Scholar 

  13. Sims GP, Ettinger R, Shirota Y, Yarboro CH, Illei GG, Lipsky PE (2005) Identification and characterization of circulating human transitional B cells. Blood 105:4390–4398

    Article  PubMed  CAS  Google Scholar 

  14. Chung JB, Silverman M, Monroe JG (2003) Transitional B cells: step by step towards immune competence. Trends Immunol 24:343–349

    Article  PubMed  CAS  Google Scholar 

  15. Martin F, Kearney JF (2002) Marginal-zone B cells. Nat Rev Immunol 2:323–335

    Article  PubMed  CAS  Google Scholar 

  16. Liu Y, Banchereau J (1996) The paths and molecular controls of peripheral B-cell development. Immunologist 4:55–66

    CAS  Google Scholar 

  17. Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, Lipsky PE, Radbruch A, Dorner T (2000) Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol 165:5970–5979

    PubMed  CAS  Google Scholar 

  18. Potter KN, Mockridge CI, Rahman A, Buchan S, Hamblin T, Davidson B, Isenberg DA, Stevenson FK (2002) Disturbances in peripheral blood B cell subpopulations in autoimmune patients. Lupus 11:872–877

    Article  PubMed  CAS  Google Scholar 

  19. Bohnhorst JO, Bjorgan MB, Thoen JE, Natvig JB, Thompson KM (2001) Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjögren’s syndrome. J Immunol 167:3610–3618

    PubMed  CAS  Google Scholar 

  20. d’Arbonneau F, Pers JO, Devauchelle V, Pennec Y, Saraux A, Youinou P (2006) BAFF-induced changes in B cell antigen receptor-containing lipid rafts in Sjögren’s syndrome. Arthritis Rheum 54:115–126

    Article  PubMed  CAS  Google Scholar 

  21. Hansen A, Gosemann M, Pruss A, Reiter K, Ruzickova S, Lipsky PE, Dorner T (2004) Abnormalities in peripheral B cell memory of patients with primary Sjögren’s syndrome. Arthritis Rheum 50:1897–1908

    Article  PubMed  CAS  Google Scholar 

  22. Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL, Saraux A, Youinou P (2006) Identification of transitional type II B cells in the salivary glands of patients with Sjögren’s syndrome. Arthritis Rheum 54:2280–2288

    Article  PubMed  CAS  Google Scholar 

  23. Koehne G, Zeller W, Stockschlaeder M, Zander AR (1997) Phenotype of lymphocyte subsets after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 19:149–156

    Article  PubMed  CAS  Google Scholar 

  24. MacLennan IC, Toellner KM, Cunningham AF, Serre K, Sze DM, Zuniga E, Cook MC, Vinuesa CG (2003) Extrafollicular antibody responses. Immunol Rev 194:8–18

    Article  PubMed  CAS  Google Scholar 

  25. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754–758

    Article  PubMed  CAS  Google Scholar 

  26. Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J, Looney RJ (2003) The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum 48:455–459

    Article  PubMed  CAS  Google Scholar 

  27. Wu J, Edberg JC, Redecha PB, Bansal V, Guyre PM, Coleman K, Salmon JE, Kimberly RP (1997) A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 100:1059–1070

    Article  PubMed  CAS  Google Scholar 

  28. Farag SS, Flinn IW, Modali R, Lehman TA, Young D, Byrd JC (2004) Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia. Blood 103:1472–1474

    Article  PubMed  CAS  Google Scholar 

  29. Pers JO, Daridon C, Devauchelle V, Jousse S, Saraux A, Jamin C, Youinou P (2005) BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci 1050:34–39

    Article  PubMed  CAS  Google Scholar 

  30. Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC (2006) Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum 54:723–732

    Article  PubMed  CAS  Google Scholar 

  31. Vallerskog T, Heimburger M, Gunnarsson I, Zhou W, Wahren-Herlenius M, Trollmo C, Malmstrom V (2006) Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther 8:R167

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Immunopathology, Brest University Medical School, Brest, France

    Jacques-Olivier Pers, Capucine Daridon, Boutahar Bendaoud, Valérie Devauchelle, Christian Berthou, Alain Saraux & Pierre Youinou

  2. Laboratory of Immunology, Brest University Medical School Hospital, BP824, 29609, Brest, France

    Pierre Youinou

Authors
  1. Jacques-Olivier Pers
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  2. Capucine Daridon
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  3. Boutahar Bendaoud
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  4. Valérie Devauchelle
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  5. Christian Berthou
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  6. Alain Saraux
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  7. Pierre Youinou
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Corresponding author

Correspondence to Pierre Youinou.

Additional information

This work was supported by a grant from the Association Française du Gougerot-Sjögren et des syndromes secs and the 2003 Clinical Research Hospital Program (PHRC 2003).

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Pers, JO., Daridon, C., Bendaoud, B. et al. B-Cell Depletion and Repopulation in Autoimmune Diseases. Clinic Rev Allerg Immunol 34, 50–55 (2008). https://doi.org/10.1007/s12016-007-8015-4

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  • DOI: https://doi.org/10.1007/s12016-007-8015-4

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