Biology of Blood and Marrow Transplantation
Volume 15, Issue 7 , Pages 795-803 , July 2009

Allogeneic Hematopoietic Stem Cell Transplantation Recipients Have Defects of Both Switched and IgM Memory B Cells

  • Lloyd J. D'Orsogna

      Affiliations

    • Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Matthew P. Wright

      Affiliations

    • Department of Haematology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Rom G. Krueger

      Affiliations

    • Flow Cytometry Unit, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Elizabeth J. McKinnon

      Affiliations

    • Centre for Clinical Immunology and Biomedical Statistics, Murdoch University and Royal Perth Hospital, Perth, Australia
    • ,
  • Susan I. Buffery

      Affiliations

    • Department of Haematology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Campbell S. Witt

      Affiliations

    • Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
    • ,
  • Nicole Staples

      Affiliations

    • Department of Haematology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Richard Loh

      Affiliations

    • Department of Clinical Immunology, Princess Margaret Hospital for Children and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Paul K. Cannell

      Affiliations

    • Department of Haematology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • ,
  • Frank T. Christiansen

      Affiliations

    • Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
    • ,
  • Martyn A. French

      Affiliations

    • Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia
    • School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
    • Corresponding Author InformationCorrespondence and reprint requests: Professor Martyn French, Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital, P.O. Box X2213, Perth, WA 6847, Australia.

Received 13 November 2008 ,Accepted 5 February 2009.

References 

  1. Storek J, Saxon A. Reconstitution of B cell immunity following bone marrow transplantation. Bone Marrow Transplant. 1992;9:395–408
  2. Witherspoon R, Storb R, Ochs H, et al. Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment. Blood. 1981;58:360–368
  3. Hammarstrom V, Pauksen K, Svensson H, et al. Serum immunoglobulin levels in relation to levels of specific antibodies in allogeneic and autologous bone marrow transplant recipients. Transplantation. 2000;69:1582–1586
  4. Engelhard D, Cordonnier C, Shaw P, et al. Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation Survey. Br J Haematol. 2002;117:444–450
  5. Winston DJ, Schiffman G, Wang DC, et al. Pneumococcal infections after human bone-marrow transplantation. Ann Intern Med. 1979;91:835–841
  6. Elias M, Bisharat N, Goldstein L, Raz R, Saliba W. Pneumococcal sepsis because of functional hyposplenism in a bone marrow transplant patient. Eur J Clin Microbiol Infect Dis. 2004;23:212–214
  7. Kulkarni S, Powles R, Treleaven J, Riley U, Singhal S, Horton C. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants. Blood. 2000;95:3683–3686
  8. Nordoy T, Husebekk A, Aaberge I, et al. Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines. Bone Marrow Transplant. 2001;28:681–687
  9. Parkkali T, Väkeväinen M, Käyhty H, Ruutu T, Ruutu P. Opsonophagocytic activity against Streptococcus pneumoniae type 19F in allogeneic BMT recipients before and after vaccination with pneumococcal polysaccharide vaccine. Bone Marrow Transplant. 2001;27:207–211
  10. Dykewicz C. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Clin Infect Dis. 2001;33:139–144
  11. Avanzini M, Carra A, Maccario R, et al. Antibody response to pneumococcal vaccine in children receiving bone marrow transplantation. J Clinical Immunol. 1995;15:137–144
  12. Picardi M, Selleri C, Rotoli B. Spleen sizing by ultrasound scan and risk of pneumococcal infection in patients with chronic GvHD: preliminary observations. Bone Marrow Transplant. 1999;24:173–177
  13. Storek J, Witherspoon R, Storb R. Reconstitution of membrane IgD− (mIgD−) B cells after marrow transplantation lag behind the reconstitution of mIgD+ B cells. Blood. 1997;89:350–351
  14. Suzuki I, Milner E, Glas A, et al. Immunoglobulin heavy chain variable region gene usage in bone marrow transplant recipients: lack of somatic mutation indicates a maturational arrest. Blood. 1996;87:1873–1880
  15. Cuss A, Avery D, Cannons J, et al. Expansion of functionally immature transitional B cells is associated with human-immunodeficient states characterized by impaired humoral immunity. J Immunol. 2006;176:1506–1516
  16. Klein U, Rajewsky K, Kuppers R. Human immunoglobulin IgM+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998;188:1679–1689
  17. Kruetzman S, Rosado M, Weber H, et al. Human immunoglobulin M memory B cells controlling streptococcus pneumoniae infections are generated in the spleen. J Exp Med. 2003;197:939–945
  18. Weller S, Braun M, Tan B, et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104:3647–3654
  19. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defence against pneumococcal bacteria by IgM memory B-cells. Immunology. 2005;175:3262–3267
  20. Steiniger B, Timphus E, Jacob R, Barth P. CD27+ B cells in human lymphatic organs: re-evaluating the splenic marginal zone. Immunology. 2005;116:429–442
  21. Waldschmidt T, Panoskaltsis-Mortari A, McElmurry R, Tygrett L, Taylor P, Blazar B. Abnormal T cell-dependent B-cell responses in SCID mice receiving allogeneic bone marrow in utero. Blood. 2002;100:4557–4564
  22. Greinix H, Pohlreich D, Kouba M, et al. Elevated numbers of immature/transitional CD21- B lymphocytes and deficiency of memory CD27+ B cells identify patients with active chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2008;14:208–219
  23. Avanzani M, Locatelli F, Dos Santos C, et al. B lymphocyte reconstitution after hematopoietic stem cell transplantation: functional immaturity and slow recovery of memory CD27+ B cells. Exp Hematol. 2005;33:480–486
  24. Lausen B, Hougs L, Schejbel L, Heilmann C, Barington T. Human memory B-cells transferred by allogeneic bone marrow transplantation contribute significantly to the antibody repertoire of the recipient. J Immunol. 2004;172:3305–3318
  25. D'Orsogna L, Krueger R, McKinnon E, French M. Memory B-cell subpopulations are affected differently by HIV infection and antiretroviral therapy. AIDS. 2007;21:1747–1752
  26. Ma C, Pittaluga S, Avery D, et al. Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease. J Clin Invest. 2006;116:322–333
  27. Di Sabatino A, Rosado M, Cazzola P, et al. Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab. Inflamm Bowel Dis. 2008;14:591–596
  28. Chong Y, Ikematsu H, Yamamoto M, et al. Increased frequency of CD27- (naïve) B cells and their phenotypic alteration in HIV type 1-infected patients. AIDS Res Hum Retroviruses. 2004;20:621–629
  29. Lanzavecchia A, Bernasconi N, Traggiai E, Ruprecht C, Corti D, Sallusto F. Understanding and making use of human memory B cells. Immunol Rev. 2006;211:303–309
  30. Wehr C, Kivioja T, Schmitt C, et al. The Euroclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85
  31. Bryant V, Ma C, Avery D, et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J Immunol. 2007;179:8180–8190
  32. Haynes N. Follicular associated T cells and their B-cell helper qualities. Tissue Antigens. 2008;71:97–104
  33. King C, Tangye S, Mackay C. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol. 2008;26:741–766
  34. Pène J, Gauchet J, Lecart S, et al. Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol. 2004;172:5154–5157
  35. Carsetti R, Rosado M, Wardmann H. Peripheral development of B cells in mouse and man. Immunol Rev. 2004;197:179–191
  36. Cinamon G, Zachariah M, Lam O, et al. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol. 2008;9:54–62
  37. Malley R, Trzcinski K, Srivastava A, et al. CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci USA. 2005;102:48–53
  38. Cuthbert R, Iqbal A, Gates A, Toghill P, Russell N. Functional hyposplenism following allogeneic bone marrow transplantation. J Clin Pathol. 1995;48:257–259
  39. Nakayama A, Hirabayashi N, Ito M, et al. White pulp reconstitution after human bone marrow transplantation. Am J Pathol. 1993;143:1111–1120
  40. Hakim F, Gress R. Reconstitution of thymic function after stem cell transplantation in humans. Curr Opin Hematol. 2002;9:490–496
  41. Komanduri K, St John L, de Lima M, et al. Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoeisis and late memory T-cell skewing. Blood. 2007;110:4543
  42. Dumont-Girard F, Roux E, van Lier R, et al. Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants. Blood. 1998;92:4464–4471
  43. Sale G, Alavaikko M, Schaefers K, Mahan C. Abnormal CD4:8 ratios and delayed germinal centre reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GvHD): an immunohistological study. Exp Hematol. 1992;20:1017–1021
  44. Durakovic N, Bezak K, Skarica M, et al. Host-derived Langerhans cells persist after MHC-matched allografting independent of donor T cells and critically influence the alloresponses mediated by donor lymphocyte infusions. J Immunol. 2006;177:4414–4425
  45. Duffner U, Maeda Y, Cooke K, et al. Host dendritic cells alone are sufficient to initiate graft-versus-host disease. J Immunol. 2004;172:7393–7398
  46. Sapoznikov A, Pewzner-Jung Y, Kalchenko V, Krauthgamer R, Shachar I, Jung S. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches. Nat Immunol. 2008;9:388–395
  47. Schneider L, Antin J, Weinstein H, et al. Lymphokine profile in bone marrow transplant recipients. Blood. 1991;78:3076–3080
  48. Velardi A, Cucciaioni S, Terenzi A, et al. Acquisition of Ig isotype diversity after bone marrow transplantation in adults. A recapitulation of normal B cell ontogeny. J Immunol. 1988;141:815–820
  49. Kelsey SM, Lowdell MW, Newland AC. IgG subclass levels and immune reconstitution after T cell-depleted allogeneic bone marrow transplantation. Clin Exp Immunol. 1990;80:409–412
  50. Rodriguez ME, van der Pol WL, Sanders LA, van de Winkel JG. Crucial role of FcgammaRIIa (CD32) in assessment of functional anti- Streptococcus pneumoniae antibody activity in human sera. J Infect Dis. 1999;179:423–433
  51. French MA, Denis KA, Dawkins R, Peter JB. Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4. Clin Exp Immunol. 1995;100:47–53
  52. Vossen J, Handgretinger R. Immune recovery and immunotherapy after stem cell transplantation in children. Bone Marrow Transplant. 2001;28S:S14–S15
  53. Perrucio K, Tosti A, Burchielli E, et al. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood. 2005;106:4397–4406
  54. Schimmelpfennig C, Schulz S, Arber C, et al. Ex vivo expanded dendritic cells home to T-cell zones of lymphoid organs and survive in vivo after allogeneic bone marrow transplantation. Am J Pathol. 2005;167:1321–1331
  55. Tangye S, Good K. Human IgM+CD27+ B cells: memory B cells or “memory” B cells?. J Immunol. 2007;179:13–19

PII: S1083-8791(08)00578-8

doi: 10.1016/j.bbmt.2008.11.024

Biology of Blood and Marrow Transplantation
Volume 15, Issue 7 , Pages 795-803 , July 2009

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