Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Apr;79(8):2663–2667. doi: 10.1073/pnas.79.8.2663

Abnormal humoral immune responses in peripheral blood lymphocyte cultures of bone marrow transplant recipients.

S G Pahwa, R N Pahwa, W Friedrich, R J O'Reilly, R A Good
PMCID: PMC346261  PMID: 6211673

Abstract

The present study was aimed at investigating recovery of humoral immunity in vitro after bone marrow transplantation in patients with acute leukemia and severe aplastic anemia. Hemolytic plaque assays were utilized to quantitate pokeweed mitogen-stimulated polyclonal immunoglobulin production and sheep erythrocyte antigen-specific antibody responses in cultures of peripheral blood mononuclear cells of 39 patients beginning at 1 month, for variable periods up to a maximum of 4 years after marrow transplantation. Three phases were identified: an early period of primary B cell dysfunction with concomitant immunoregulatory T cell abnormalities--i.e., decreased helper and increased suppressor activities; an intermediate phase in which B cell dysfunction could be attributed in large measure to immunoregulatory T cell abnormalities; and a late phase of normal B and T lymphocyte functions. Patients with graft-versus-host disease differed from those without it in that they often did not manifest increased T cell suppressor activity in the early period, and they were noted to have prolonged and profound B and T cell abnormalities in the chronic phase of their disease. In selected patients, simultaneous assessment of ratios of Leu-2 to Leu-3 antigens on T cells by monoclonal antibodies and of immunoregulatory T cell functions revealed a correlation between the two only late in the post-transplant period. These studies provide an insight into the ontogeny of B cell function in the post-transplant period and indicate that in certain situations phenotypic alterations in T cell subsets cannot reliably be used to predict abnormalities in their function in recipients of marrow transplantation.

Full text

PDF
2663

Images in this article

2664Image
on p.2664
2664Image
on p.2664
2665Image
on p.2665
2665Image
on p.2665
2665Image
on p.2665
2666Image
on p.2666

Selected References

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

  1. Atkinson K., Storb R., Prentice R. L., Weiden P. L., Witherspoon R. P., Sullivan K., Noel D., Thomas E. D. Analysis of late infections in 89 long-term survivors of bone marrow transplantation. Blood. 1979 Apr;53(4):720–731. [PubMed] [Google Scholar]
  2. Dosch H. M., Gelfand E. W. Failure of T and B cell cooperation during graft-versus-host disease. Transplantation. 1981 Jan;31(1):48–50. doi: 10.1097/00007890-198101000-00011. [DOI] [PubMed] [Google Scholar]
  3. Elfenbein G. J., Anderson P. N., Humphrey R. L., Mullins G. M., Sensenbrenner L. L., Wands J. R., Santos G. W. Immune system reconstitution following allogeneic bone marrow transplantation in man: a multiparameter analysis. Transplant Proc. 1976 Dec;8(4):641–646. [PubMed] [Google Scholar]
  4. Engleman E. G., Benike C. J., Glickman E., Evans R. L. Antibodies to membrane structures that distinguish suppressor/cytotoxic and helper T lymphocyte subpopulations block the mixed leukocyte reaction in man. J Exp Med. 1981 Jul 1;154(1):193–198. doi: 10.1084/jem.154.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Evans R. L., Wall D. W., Platsoucas C. D., Siegal F. P., Fikrig S. M., Testa C. M., Good R. A. Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen. Proc Natl Acad Sci U S A. 1981 Jan;78(1):544–548. doi: 10.1073/pnas.78.1.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Glucksberg H., Storb R., Fefer A., Buckner C. D., Neiman P. E., Clift R. A., Lerner K. G., Thomas E. D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295–304. doi: 10.1097/00007890-197410000-00001. [DOI] [PubMed] [Google Scholar]
  9. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  10. Hoffmann M. K. Antigen-specific induction and regulation of antibody synthesis in cultures of human peripheral blood mononuclear cells. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1139–1143. doi: 10.1073/pnas.77.2.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  12. Ledbetter J. A., Evans R. L., Lipinski M., Cunningham-Rundles C., Good R. A., Herzenberg L. A. Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med. 1981 Feb 1;153(2):310–323. doi: 10.1084/jem.153.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Pahwa S. G., Pahwa R. N., Good R. A. Decreased in vitro humoral immune responses in aged humans. J Clin Invest. 1981 Apr;67(4):1094–1102. doi: 10.1172/JCI110122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pahwa S., Shou L., Pahwa R., Smithwick E., Good R. A. Influence of human thymocytes on B-lymphocyte differentiation in man. Cell Immunol. 1979 May;44(2):433–441. doi: 10.1016/0008-8749(79)90018-2. [DOI] [PubMed] [Google Scholar]
  17. Reinherz E. L., Parkman R., Rappeport J., Rosen F. S., Schlossman S. F. Aberrations of suppressor T cells in human graft-versus-host disease. N Engl J Med. 1979 May 10;300(19):1061–1068. doi: 10.1056/NEJM197905103001901. [DOI] [PubMed] [Google Scholar]
  18. Rieger M., Hilgert I. The involvement of a suppressor mechanism in neonatally induced allograft tolerance in mice. J Immunogenet. 1977 Feb;4(1):61–67. doi: 10.1111/j.1744-313x.1977.tb00615.x. [DOI] [PubMed] [Google Scholar]
  19. Ringden O., Witherspoon R., Storb R., Ekelund E., Thomas E. D. B cell function in human marrow transplant recipients assessed by direct and indirect hemolysis-in-gel assays. J Immunol. 1979 Dec;123(6):2729–2734. [PubMed] [Google Scholar]
  20. Slavin R. E., Woodruff J. M. The pathology of bone marrow transplantation. Pathol Annu. 1974;9(0):291–344. [PubMed] [Google Scholar]
  21. Storb R. Decrease in the graft rejection rate and improvement in survival after marrow transplantation for severe aplastic anemia. Transplant Proc. 1979 Mar;11(1):196–198. [PubMed] [Google Scholar]
  22. Storb R., Thomas E. D., Buckner C. D., Clift R. A., Fefer A., Fernando L. P., Giblett E. R., Johnson F. L., Neiman P. E. Allogeneic marrow grafting for treatment of aplastic anemia: a follow-up on long-term survivors. Blood. 1976 Oct;48(4):485–490. [PubMed] [Google Scholar]
  23. Thomas E. D., Buckner C. D., Banaji M., Clift R. A., Fefer A., Flournoy N., Goodell B. W., Hickman R. O., Lerner K. G., Neiman P. E. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977 Apr;49(4):511–533. [PubMed] [Google Scholar]
  24. Thomas E. D., Fefer A., Buckner C. D., Storb R. Current status of bone marrow transplantation for aplastic anemia and acute leukemia. Blood. 1977 May;49(5):671–681. [PubMed] [Google Scholar]
  25. Thomas E. D., Storb R., Clift R. A., Fefer A., Johnson L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895–902. doi: 10.1056/NEJM197504242921706. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Umiel T., Globerson A., Trainin N. Development of immunosuppressor cells. Exertion of specific suppression by neonatal liver cells. Transplantation. 1977 Oct;24(4):282–289. doi: 10.1097/00007890-197710000-00008. [DOI] [PubMed] [Google Scholar]
  28. Wang C. Y., Good R. A., Ammirati P., Dymbort G., Evans R. L. Identification of a p69,71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells. J Exp Med. 1980 Jun 1;151(6):1539–1544. doi: 10.1084/jem.151.6.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winston D. J., Gale R. P., Meyer D. V., Young L. S. Infectious complications of human bone marrow transplantation. Medicine (Baltimore) 1979 Jan;58(1):1–31. doi: 10.1097/00005792-197901000-00001. [DOI] [PubMed] [Google Scholar]
  30. Winston D. J., Schiffman G., Wang D. C., Feig S. A., Lin C. H., Marso E. L., Ho W. G., Young L. S., Gale R. P. Pneumococcal infections after human bone-marrow transplantation. Ann Intern Med. 1979 Dec;91(6):835–841. doi: 10.7326/0003-4819-91-6-835. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Witherspoon R., Noel D., Storb R., Ochs H. D., Thomas E. D. The effect of graft-versus-host disease on reconstitution of the immune system following marrow transplantation for aplastic anemia or leukemia. Transplant Proc. 1978 Mar;10(1):233–235. [PubMed] [Google Scholar]
  33. de Bruin H. G., Astaldi A., Leupers T., van de Griend R. J., Dooren L. J., Schellekens P. T., Tanke H. J., Roos M., Vossen J. M. T lymphocyte characteristics in bone marrow-transplanted patients. II. Analysis with monoclonal antibodies. J Immunol. 1981 Jul;127(1):244–251. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES