Biology of Blood and Marrow Transplantation
Volume 16, Issue 9 , Pages 1222-1230 , September 2010

Recipient B Cells Are Not Required for Graft-Versus-Host Disease Induction

  • Catherine Matte-Martone

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
    • Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Xiajian Wang

      Affiliations

    • Institute of Immunology, Zhejiang University, Hangzhou, People's Republic of China
    • ,
  • Britt Anderson

      Affiliations

    • Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Dhanpat Jain

      Affiliations

    • Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Anthony J. Demetris

      Affiliations

    • Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • ,
  • Jennifer McNiff

      Affiliations

    • Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Mark J. Shlomchik

      Affiliations

    • Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
    • Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Warren D. Shlomchik

      Affiliations

    • Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
    • Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
    • Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
    • Corresponding Author InformationCorrespondence and reprint requests: Warren D. Shlomchik, MD, Medical Oncology and Immunobiology, Yale University of Medicine, P.O. Box 208032, New Haven, CT 06620.

Received 18 January 2010 ,Accepted 16 March 2010.

References 

  1. Shlomchik WD, Couzens MS, Tang CB, et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science. 1999;285:412–415
  2. Anderson BE, McNiff JM, Jain D, Blazar BR, Shlomchik WD, Shlomchik MJ. Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease: requirements depend on target organ. Blood. 2005;105:2227–2234
  3. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100
  4. Teshima T, Ordemann R, Reddy P, et al. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat Med. 2002;8:575–581
  5. Duffner UA, Maeda Y, Cooke KR, et al. Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease. J Immunol. 2004;172:7393–7398
  6. Schultz KR, Paquet J, Bader S, HayGlass KT. Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease. Bone Marrow Transplant. 1995;16:289–295
  7. Maloney DG. Preclinical and phase I and II trials of rituximab. Semin Oncol. 1999;26:74–78
  8. Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol. 2006;6:394–403
  9. Ratanatharathorn V, Ayash L, Reynolds C, et al. Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody. Biol Blood Marrow Transplant. 2003;9:505–511
  10. Cutler C, Miklos D, Kim HT, et al. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006;108:756–762
  11. Miklos DB, Kim HT, Miller KH, et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood. 2005;105:2973–2978
  12. Khouri IF, Keating M, Korbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16:2817–2824
  13. Khouri IF, Saliba RM, Giralt SA, et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001;98:3595–3599
  14. Zhong G, Reis e Sousa C, Germain RN. Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro. J Exp Med. 1997;186:673–682
  15. Bogen B, Weiss S. Processing and presentation of idiotypes to MHC-restricted T cells. Int Rev Immunol. 1993;10:337–355
  16. Sant AJ. Endogenous antigen presentation by MHC class II molecules. Immunol Res. 1994;13:253–267
  17. Brooks AG, McCluskey J. Class II-restricted presentation of a hen egg lysozyme determinant derived from endogenous antigen sequestered in the cytoplasm or endoplasmic reticulum of the antigen presenting cells. J Immunol. 1993;150:3690–3697
  18. Munthe LA, Kyte JA, Bogen B. Resting small B cells present endogenous immunoglobulin variable-region determinants to idiotope-specific CD4(+) T cells in vivo. Eur J Immunol. 1999;29:4043–4052
  19. Constant S, Schweitzer N, West J, Ranney P, Bottomly K. B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo. J Immunol. 1995;155:3734–3741
  20. Croft M, Duncan DD, Swain SL. Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements. J Exp Med. 1992;176:1431–1437
  21. Croft M, Bradley LM, Swain SL. Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J Immunol. 1994;152:2675–2685
  22. Ron Y, Sprent J. T cell priming in vivo: a major role for B cells in presenting antigen to T cells in lymph nodes. J Immunol. 1987;138:2848–2856
  23. Ke Y, Kapp JA. Exogenous antigens gain access to the major histocompatibility complex class I processing pathway in B cells by receptor-mediated uptake. J Exp Med. 1996;184:1179–1184
  24. Yefenof E, Zehavi-Feferman R, Guy R. Control of primary and secondary antibody responses by cytotoxic T lymphocytes specific for a soluble antigen. Eur J Immunol. 1990;20:1849–1853
  25. Barnaba V, Franco A, Alberti A, Benvenuto R, Balsano F. Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes. Nature. 1990;345:258–260
  26. Shen H, Whitmire JK, Fan X, Shedlock DJ, Kaech SM, Ahmed R. A specific role for B cells in the generation of CD8 T cell memory by recombinant Listeria monocytogenes. J Immunol. 2003;170:1443–1451
  27. Epstein MM, Di Rosa F, Jankovic D, Sher A, Matzinger P. Successful T cell priming in B cell-deficient mice. J Exp Med. 1995;182:915–922
  28. Asano MS, Ahmed R. CD8 T cell memory in B cell-deficient mice. J Exp Med. 1996;183:2165–2174
  29. Bennett SR, Carbone FR, Toy T, Miller JF, Heath WR. B cells directly tolerize CD8(+) T cells. J Exp Med. 1998;188:1977–1983
  30. Fuchs EJ, Matzinger P. B cells turn off virgin but not memory T cells. Science. 1992;258:1156–1159
  31. Hollsberg P, Batra V, Dressel A, Hafler DA. Induction of anergy in CD8 T cells by B cell presentation of antigen. J Immunol. 1996;157:5269–5276
  32. Fu YX, Huang G, Wang Y, Chaplin DD. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion. J Exp Med. 1998;187:1009–1018
  33. Ngo VN, Korner H, Gunn MD, et al. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med. 1999;189:403–412
  34. Kabashima K, Banks TA, Ansel KM, Lu TT, Ware CF, Cyster JG. Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity. 2005;22:439–450
  35. Kitamura D, Rajewsky K. Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion. Nature. 1992;356:154–156
  36. Chen J, Trounstine M, Alt FW, et al. Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol. 1993;5:647–656
  37. Ahuja A, Shupe J, Dunn R, Kashgarian M, Kehry MR, Shlomchik MJ. Depletion of B cells in murine lupus: efficacy and resistance. J Immunol. 2007;179:3351–3361
  38. Anderson BE, McNiff J, Yan J, et al. Memory CD4+ T cells do not induce graft-versus-host disease. J Clin Invest. 2003;112:101–108
  39. Matte-Martone C, Liu J, Jain D, McNiff J, Shlomchik WD. CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL. Blood. 2008;111:3884–3892
  40. Beilhack A, Schulz S, Baker J, et al. Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs. Blood. 2008;111:2919–2928
  41. Anderson BE, Taylor PA, McNiff JM, et al. Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood. 2008;111:5242–5251
  42. Hamilton BL, Bevan MJ, Parkman R. Anti-recipient cytotoxic T lymphocyte precursors are present in the spleens of mice with acute graft versus host disease due to minor histocompatibility antigens. J Immunol. 1981;126:621–625
  43. Kaplan DH, Anderson BE, McNiff JM, Jain D, Shlomchik MJ, Shlomchik WD. Target antigens determine graft-versus-host disease phenotype. J Immunol. 2004;173:5467–5475
  44. Allman DM, Ferguson SE, Cancro MP. Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhi and exhibit unique signaling characteristics. J Immunol. 1992;149:2533–2540
  45. Allman DM, Ferguson SE, Lentz VM, Cancro MP. Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells. J Immunol. 1993;151:4431–4444
  46. Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 2006;176:705–710
  47. Hu CY, Rodriguez-Pinto D, Du W, et al. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest. 2007;117:3857–3867
  48. Rowe V, Banovic T, MacDonald KP, et al. Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation. Blood. 2006;108:2485–2492
  49. Kebriaei P, Saliba RM, Ma C, et al. Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia. Bone Marrow Transplant. 2006;38:203–209
  50. van Dorp S, Pietersma F, Wölfl M, et al. Rituximab treatment before reduced-intensity conditioning transplantation associates with a decreased incidence of extensive chronic GVHD. Biol Blood Marrow Transplant. 2009;15:671–678
  51. Bellucci R, Alyea EP, Chiaretti S, et al. Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor. Blood. 2005;105:3945–3950
  52. Zorn E, Miklos DB, Floyd BH, et al. Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation. J Exp Med. 2004;199:1133–1142
  53. Zhang C, Todorov I, Zhang Z, et al. Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestations. Blood. 2006;107:2993–3001

 C.M., X.W., and B.A. contributed equally to this article.

 Financial disclosure: See Acknowledgments on page 1229.

PII: S1083-8791(10)00121-7

doi: 10.1016/j.bbmt.2010.03.015

Biology of Blood and Marrow Transplantation
Volume 16, Issue 9 , Pages 1222-1230 , September 2010

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