Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Mar 1;161(3):563–576. doi: 10.1084/jem.161.3.563

Bone marrow graft rejection as a function of antibody-directed natural killer cells

PMCID: PMC2187585  PMID: 2579185

Abstract

There is conclusive evidence that acute bone marrow transplant rejection in lethally irradiated mice is caused by natural killer (NK) cells. The rejection of marrow allografts is exquisitely specific and is controlled by antigenic determinants encoded in or near the H-2 gene complex. The specificity of in vivo marrow graft rejection contrasts with the in vitro specificity pattern of NK cells in cytotoxicity assays. We therefore examined how NK cells cause H-2-specific marrow graft rejection in vivo. Several experimental approaches are presented that suggest that natural antibody, present in responder strains of mice, specifically directs NK cells in an antibody-dependent cytolytic and/or cytostatic reaction, resulting in marrow graft rejection. The following evidence for this mechanism is documented. The ability to reject a marrow graft can be passively transferred by serum from responder to allogeneic nonresponder mice and the specificity of rejection can be mapped within the H-2 region. Serum-induced marrow graft rejection is abrogated following depletion of immunoglobulin, and the serum of responder mice is able to induce a specific antibody- dependent cytotoxic reaction in vitro.

Full Text

The Full Text of this article is available as a PDF (886.3 KB).

Selected References

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

  1. Bradley T. P., Bonavida B. Mechanism of cell-mediated cytotoxicity at the single cell level. IV. Natural killing and antibody-dependent cellular cytotoxicity can be mediated by the same human effector cell as determined by the two-target conjugate assay. J Immunol. 1982 Nov;129(5):2260–2265. [PubMed] [Google Scholar]
  2. CUDKOWICZ G., STIMPFLING J. H. INDUCTION OF IMMUNITY AND OF UNRESPONSIVENESS TO PARENTAL MARROW GRAFTS IN ADULT F-1 HYBRID MICE. Nature. 1964 Oct 31;204:450–453. doi: 10.1038/204450a0. [DOI] [PubMed] [Google Scholar]
  3. Chow D. A., Wolosin L. B., Greenberg A. H. Genetics, regulation, and specificity of murine natural antitumor antibodies and natural killer cells. J Natl Cancer Inst. 1981 Aug;67(2):445–453. [PubMed] [Google Scholar]
  4. Chow D. A., Wolosin L. B., Greenberg A. H. Murine natural anti-tumor antibodies. II. The contribution of natural antibodies to tumor surveillance. Int J Cancer. 1981;27(4):459–469. doi: 10.1002/ijc.2910270407. [DOI] [PubMed] [Google Scholar]
  5. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice. J Exp Med. 1971 Jul 1;134(1):83–102. doi: 10.1084/jem.134.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J Exp Med. 1971 Dec 1;134(6):1513–1528. doi: 10.1084/jem.134.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cudkowicz G. Genetic control of bone marrow graft rejection. I. Determinant-specific difference of reactivity in two pairs of inbred mouse strains. J Exp Med. 1971 Jul 1;134(1):281–293. doi: 10.1084/jem.134.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cudkowicz G. Genetic control of resistance to allogeneic and xenogeneic bone-marrow grafts in mice. Transplant Proc. 1975 Jun;7(2):155–159. [PubMed] [Google Scholar]
  9. Cudkowicz G., Lotzová E. Hemopoietic cell-defined components of the major histocompatibility complex of mice: identification of responsive and unresponsive recipients for bone marrow transplants. Transplant Proc. 1973 Dec;5(4):1399–1405. [PubMed] [Google Scholar]
  10. Dennert G., Yogeeswaran G., Yamagata S. Cloned cell lines with natural killer activity. Specificity, function, and cell surface markers. J Exp Med. 1981 Mar 1;153(3):545–556. doi: 10.1084/jem.153.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Drizlikh G., Schmidt-Sole J., Yankelevich B. Involvement of the K and I regions of the H-2 complex in resistance to hemopoietic allografts. J Exp Med. 1984 Apr 1;159(4):1070–1082. doi: 10.1084/jem.159.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grönberg A., Hansson M., Kiessling R., Andersson B., Kärre K., Roder J. Demonstration of natural antibodies in normal rabbit serum with similar specificity pattern as mouse natural killer cells. J Natl Cancer Inst. 1980 May;64(5):1113–1119. [PubMed] [Google Scholar]
  13. Kiessling R., Hochman P. S., Haller O., Shearer G. M., Wigzell H., Cudkowicz G. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol. 1977 Sep;7(9):655–663. doi: 10.1002/eji.1830070915. [DOI] [PubMed] [Google Scholar]
  14. Klein M., Roder J., Haliotis T., Korec S., Jett J. R., Herberman R. B., Katz P., Fauci A. S. Chédiak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody-dependent cell-mediated cytotoxicity function. J Exp Med. 1980 May 1;151(5):1049–1058. doi: 10.1084/jem.151.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ménard S., Colnaghi M. I., Porta G. D. Natural anti-tumor serum reactivity in BALB/c mice. I. Characterization and interference with tumor growth. Int J Cancer. 1977 Feb 15;19(2):267–274. doi: 10.1002/ijc.2910190217. [DOI] [PubMed] [Google Scholar]
  16. Nakano K., Nakamura I., Cudkowicz G. Generation of F1 hybrid cytotoxic T lymphocytes specific for self H-2. Nature. 1981 Feb 12;289(5798):559–563. doi: 10.1038/289559a0. [DOI] [PubMed] [Google Scholar]
  17. Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
  18. Parkinson D. R., Brightman R. P., Waksal S. D. Altered natural killer cell biology in C57BL/6 mice after leukemogenic split-dose irradiation. J Immunol. 1981 Apr;126(4):1460–1464. [PubMed] [Google Scholar]
  19. Ralph P., Nakoinz I. Cell-mediated lysis of tumor targets directed by murine monoclonal antibodies of IgM and all IgG isotypes. J Immunol. 1983 Aug;131(2):1028–1031. [PubMed] [Google Scholar]
  20. Risser R., Grunwald D. J. Production of anti-self H-2 antibodies by hybrid mice immune to a viral tumour. Nature. 1981 Feb 12;289(5798):563–568. doi: 10.1038/289563a0. [DOI] [PubMed] [Google Scholar]
  21. Roder J. C., Lohmann-Matthes M. L., Domzig W., Wigzell H. The beige mutation in the mouse. II. Selectivity of the natural killer (NK) cell defect. J Immunol. 1979 Nov;123(5):2174–2181. [PubMed] [Google Scholar]
  22. Roder J. C. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J Immunol. 1979 Nov;123(5):2168–2173. [PubMed] [Google Scholar]
  23. Roder J., Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979 Mar 29;278(5703):451–453. doi: 10.1038/278451a0. [DOI] [PubMed] [Google Scholar]
  24. Talmadge J. E., Meyers K. M., Prieur D. J., Starkey J. R. Role of NK cells in tumour growth and metastasis in beige mice. Nature. 1980 Apr 17;284(5757):622–624. doi: 10.1038/284622a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES