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. 1986 Oct;78(4):959–967. doi: 10.1172/JCI112686

Designed transfer of specific immune responses with bone marrow transplantation.

A Saxon, R Mitsuyasu, R Stevens, R E Champlin, H Kimata, R P Gale
PMCID: PMC423731  PMID: 3531239

Abstract

Bone marrow transplant donors were immunized with tetanus/diphtheria toxoids 6-7 d before bone marrow donation to investigate the role of B cell subpopulations in reconstitution of humoral immunity. Lymphoblastoid B cells spontaneously producing IgG antitetanus and/or antidiphtheria toxoid were detected in the donor marrows at the time of transplantation. Recipients rapidly demonstrated 3-90-fold increases in serum IgG antitetanus and antidiphtheria toxoid levels. Antidiphtheria fragment A antibody in three donor/recipient pairs demonstrated spectrotypic identity indicating transfer of the donors' response. Reimmunization of three recipients 64-154 d after transplant revealed an IgG antibody response associated with reappearance of spontaneous antibody-producing B cells and an antidiphtheria fragment A response characteristics of the donor's immune response. These observations extend the understanding of the role of B cell subpopulations and provide a basis for specific modulation of immunity in the setting of bone marrow transplantation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler L. T., Adler F. L. Immunocompetence of chimeric rabbits. I. Participation of donor-derived B lymphocytes in immunoglobulin, but not in antibody, synthesis. Transplantation. 1984 Oct;38(4):382–386. doi: 10.1097/00007890-198410000-00013. [DOI] [PubMed] [Google Scholar]
  2. Atkinson K., Farewell V., Storb R., Tsoi M. S., Sullivan K. M., Witherspoon R. P., Fefer A., Clift R., Goodell B., Thomas E. D. Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood. 1982 Sep;60(3):714–720. [PubMed] [Google Scholar]
  3. Brieva J. A., Stevens R. H. Human in vivo antigen-induced lymphoblastoid B cells are capable of cyclical antibody production in vitro. J Immunol. 1984 Jul;133(1):147–153. [PubMed] [Google Scholar]
  4. CHIN P. H., SILVERMAN M. S. Studies on the transfer of antibody formation by iso- and heterotransplants. J Immunol. 1960 Aug;85:120–129. [PubMed] [Google Scholar]
  5. Fass L., Ochs H. D., Thomas E. D., Mickelson E., Storb R., Fefer A. Studies of immunological reactivity following syngeneic or allogeneic marrow grafts in man. Transplantation. 1973 Dec;16(6):630–640. doi: 10.1097/00007890-197312000-00015. [DOI] [PubMed] [Google Scholar]
  6. Friedrich W., O'Reilly R. J., Koziner B., Gebhard D. F., Jr, Good R. A., Evans R. L. T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions. Blood. 1982 Apr;59(4):696–701. [PubMed] [Google Scholar]
  7. GARVER R. M., SANTOS G. W., COLE L. J. Specific hemagglutinins in x-irradiated, bone-marrow treated mice following differential immunization of host and donor. J Immunol. 1959 Jul;83(1):57–65. [PubMed] [Google Scholar]
  8. GENGOZIAN N., MAKINODAN T., SHEKARCHI I. C. Transplantation of antibody-forming cells in lethally irradiated mice. J Immunol. 1961 Feb;86:113–122. [PubMed] [Google Scholar]
  9. Gale R. P., Opelz G., Mickey M. R., Graze P. R., Saxon A. Immunodeficiency following allogeneic bone marrow transplantation. Transplant Proc. 1978 Mar;10(1):223–227. [PubMed] [Google Scholar]
  10. Gill D. M., Dinius L. L. Observations on the structure of diphtheria toxin. J Biol Chem. 1971 Mar 10;246(5):1485–1491. [PubMed] [Google Scholar]
  11. Gratama J. W., Naipal A., Oljans P., Zwaan F. E., Verdonck L. F., de Witte T., Vossen J. M., Bolhuis R. L., de Gast G. C., Jansen J. T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease. Blood. 1984 Jun;63(6):1416–1423. [PubMed] [Google Scholar]
  12. Kodo H., Gale R. P., Saxon A. Antibody synthesis by bone marrow cells in vitro following primary and booster tetanus toxoid immunization in humans. J Clin Invest. 1984 May;73(5):1377–1384. doi: 10.1172/JCI111341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lum L. G., Seigneuret M. C., Orcutt-Thordarson N., Noges J. E., Storb R. The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting. Blood. 1985 Jun;65(6):1422–1433. [PubMed] [Google Scholar]
  14. Lum L. G., Seigneuret M. C., Storb R. F., Witherspoon R. P., Thomas E. D. In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease. Blood. 1981 Sep;58(3):431–439. [PubMed] [Google Scholar]
  15. Meyers J. D., Flournoy N., Thomas E. D. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis. 1982 Nov-Dec;4(6):1119–1132. doi: 10.1093/clinids/4.6.1119. [DOI] [PubMed] [Google Scholar]
  16. Morrow C. D., Dorey F., Stevens R. H. Isoelectric focusing of human anti-diphtheria toxoid antibodies: identical spectrotypes of anti-fragment A antibodies with the same IgG subclass and light chain constant regions are expressed in multiple individuals. J Immunol. 1983 Feb;130(2):818–823. [PubMed] [Google Scholar]
  17. Morrow C. D., Macy E. M., Stevens R. H. Analysis of human anti-diphtheria antibodies by isoelectric focusing: evidence for restricted clonal heterogeneity of anti-fragment A antibodies. Infect Immun. 1981 Mar;31(3):1132–1137. doi: 10.1128/iai.31.3.1132-1137.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morrow C. D., Macy E. M., Stevens R. H. Analysis of human anti-diphtheria antibodies by isoelectric focusing: evidence for restricted clonal heterogeneity of anti-fragment A antibodies. Infect Immun. 1981 Mar;31(3):1132–1137. doi: 10.1128/iai.31.3.1132-1137.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noel D. R., Witherspoon R. P., Storb R., Atkinson K., Doney K., Mickelson E. M., Ochs H. D., Warren R. P., Weiden P. L., Thomas E. D. Does graft-versus-host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors. Blood. 1978 Jun;51(6):1087–1105. [PubMed] [Google Scholar]
  20. Noel D. R., Witherspoon R. P., Storb R., Atkinson K., Doney K., Mickelson E. M., Ochs H. D., Warren R. P., Weiden P. L., Thomas E. D. Does graft-versus-host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors. Blood. 1978 Jun;51(6):1087–1105. [PubMed] [Google Scholar]
  21. Pahwa S. G., Pahwa R. N., Friedrich W., O'Reilly R. J., Good R. A. Abnormal humoral immune responses in peripheral blood lymphocyte cultures of bone marrow transplant recipients. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2663–2667. doi: 10.1073/pnas.79.8.2663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Paulin T., Ringdén O., Lönnqvist B. Faster immunological recovery after bone marrow transplantation in patients without cytomegalovirus infection. Transplantation. 1985 Apr;39(4):377–384. doi: 10.1097/00007890-198504000-00008. [DOI] [PubMed] [Google Scholar]
  23. STONER R. D., BOND V. P. ANTIBODY FORMATION BY TRANSPLANTED BONE MARROW, SPLEEN, LYMPH NODES AND THYMUS CELLS IN IRRADIATED RECIPIENTS. J Immunol. 1963 Aug;91:185–196. [PubMed] [Google Scholar]
  24. Saarinen U. M. Transfer of latent atopy by bone marrow transplantation? A case report. J Allergy Clin Immunol. 1984 Aug;74(2):196–200. doi: 10.1016/0091-6749(84)90286-0. [DOI] [PubMed] [Google Scholar]
  25. Schroff R. W., Gale R. P., Fahey J. L. Regeneration of T cell subpopulations after bone marrow transplantation: cytomegalovirus infection and lymphoid subset imbalance. J Immunol. 1982 Nov;129(5):1926–1930. [PubMed] [Google Scholar]
  26. Stevens R. H., Macy E., Morrow C., Saxon A. Characterization of a circulating subpopulation of spontaneous antitetanus toxoid antibody producing B cells following in vivo booster immunization. J Immunol. 1979 Jun;122(6):2498–2504. [PubMed] [Google Scholar]
  27. Stevens R. H., Saxon A. Differential synthesis of IgM and IgA anti-tetanus toxoid antibody in vitro following in vivo booster immunization of humans. Cell Immunol. 1979 Jun;45(1):142–150. doi: 10.1016/0008-8749(79)90369-1. [DOI] [PubMed] [Google Scholar]
  28. Stevens R. H., Saxon A. Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization. J Clin Invest. 1978 Dec;62(6):1154–1160. doi: 10.1172/JCI109234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stevens R. H., Tamaroff M., Saxon A. Inability of patients with common variable hypogammaglobulinemia to generate lymphjoblastoid B cells following booster immunization. Clin Immunol Immunopathol. 1980 Jul;16(3):336–343. doi: 10.1016/0090-1229(80)90139-7. [DOI] [PubMed] [Google Scholar]
  30. Tsoi M. S., Storb R., Dobbs S., Kopecky K. J., Santos E., Weiden P. L., Thomas E. D. Nonspecific suppressor cells in patients with chronic graft-vs-host disease after marrow grafting. J Immunol. 1979 Nov;123(5):1970–1976. [PubMed] [Google Scholar]
  31. Tucker J., Barnetson R. S., Eden O. B. Atopy after bone marrow transplantation. Br Med J (Clin Res Ed) 1985 Jan 12;290(6462):116–117. doi: 10.1136/bmj.290.6462.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wahren B., Gahrton G., Linde A., Ljungman P., Lönnqvist B., Ringdén O., Sundqvist V. A. Transfer and persistence of viral antibody-producing cells in bone marrow transplantation. J Infect Dis. 1984 Sep;150(3):358–365. doi: 10.1093/infdis/150.3.358. [DOI] [PubMed] [Google Scholar]
  33. Wimperis J. Z., Brenner M. K., Prentice H. G., Reittie J. E., Karayiannis P., Griffiths P. D., Hoffbrand A. V. Transfer of a functioning humoral immune system in transplantation of T-lymphocyte-depleted bone marrow. Lancet. 1986 Feb 15;1(8477):339–343. doi: 10.1016/s0140-6736(86)92315-9. [DOI] [PubMed] [Google Scholar]
  34. Winston D. J., Ho W. G., Schiffman G., Champlin R. E., Feig S. A., Gale R. P. Pneumococcal vaccination of recipients of bone marrow transplants. Arch Intern Med. 1983 Sep;143(9):1735–1737. [PubMed] [Google Scholar]
  35. Witherspoon R. P., Kopecky K., Storb R. F., Flournoy N., Sullivan K. M., Sosa R., Deeg H. J., Ochs H. D., Cheever M. A., Fefer A. Immunological recovery in 48 patients following syngeneic marrow transplantation or hematological malignancy. Transplantation. 1982 Feb;33(2):143–149. doi: 10.1097/00007890-198202000-00008. [DOI] [PubMed] [Google Scholar]
  36. Witherspoon R. P., Matthews D., Storb R., Atkinson K., Cheever M., Deeg H. J., Doney K., Kalbfleisch J., Noel D., Prentice R. Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease. Transplantation. 1984 Feb;37(2):145–150. doi: 10.1097/00007890-198402000-00006. [DOI] [PubMed] [Google Scholar]
  37. Witherspoon R. P., Storb R., Ochs H. D., Fluornoy N., Kopecky K. J., Sullivan K. M., Deeg J. H., Sosa R., Noel D. R., Atkinson K. 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 Aug;58(2):360–368. [PubMed] [Google Scholar]

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