Advertisement

Immunogenetics

, Volume 10, Issue 1–4, pp 273–281 | Cite as

Bone-marrow-cell grafts involving theH-2D andH-2L mutant haplotypes

  • Michael Bennett
  • Roger W. Melvold
  • Henry I. Kohn
Original Investigations

Abstract

TwoH-2 d mutants,H-2 dm2 (H-2L loss mutation) andH-2dm1 (gainplus-loss mutation involving bothH-2L andH-2D) were evaluated for any change in the immunogenicity of marrow stem cells. Grafts of 2 or 4 × 106 BALB/c(C) or BALB/c-H-2dm2 (C-H-2 dm 2) marrow cells were accepted by lethally irradiated B10.D2(H-2 d ) recipients and were rejected by irradiated B10(H-2 b ) recipients. Moreover, both (B6 × C)F1 and (B6 × C-H-2 dm 2)F1 mice, as irradiated recipients, resisted the growth of parental-strain B6(H-2 b ) marrow cells but accepted grafts from C or C-H-2 dm 2 parental-strain donors. Thus, theH-2 mutation involvingH-2L but notH-2D did not affect the expression ofH-2 d -associated Hemopoietic or Hybrid(Hh) antigens of marrow stem cells. Grafts of 2 to 8 × 106 B10.D2 or B10.D2-H-2 dm 1 marrow cells were rejected by B10.BR(H-2 k ) and B6 hosts and were accepted by B10.D2 hosts. However, B10.D2-H-2 dm 1 marrow cells grew to a much greater extent than B10.D2 cells in irradiated (B6 × B10.D2)F1 or (B6 × B10.D2-H-2 dm 1)F1 host mice. Therefore, theH-2 dm 1 mutation has altered the expression of Hh antigens at least quantitatively, resulting in a relative loss of “hybrid resistance” with the retention of Hh determinants recognized by allogeneic recipient mice which are notH-2 d . Since the Hh determinants of B10.D2 marrow cells have been mapped 16 cM to the right ofH-2, this mutation atH-2D/H-2L may have affected a regulatory gene.

Keywords

Stem Cell Regulatory Gene Marrow Cell Recipient Mouse Relative Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bennett, M.: Rejection of marrow allografts. Importance of H-2 homozygosity of donor cells.Transplantation 14: 289–298, 1972PubMedGoogle Scholar
  2. Bennett, M. Cudkowicz, G., Foster, R. S., Jr., and Metcalf, D.: Hemopoietic progenitor cells of Wanemic mice studied in vivo in vitro.J. Cell. Physiol. 71: 211–226, 1968PubMedGoogle Scholar
  3. Clark, E. A., Harmon, R. C., and Wicker, L. S.: Resistance of H-2 heterozygous mice to parental tumors II. Characterization of Hh-1-controlled hybrid resistance to syngeneic fibrosarcomas and the EL-4 lymphoma.J. Immunol. 119: 648–656, 1977Google Scholar
  4. Cudkowicz, G.: Hybrid resistance and parental specific transplantation antigens.In R. N. Rose andF. Milgrom (eds.):International Convocation on Immunology, pp. 193–202, S. Karger, Basel, Switzerland 1968Google Scholar
  5. Cudkowicz, G.: Genetic regulation of bone marrow allograft rejection in mice.In S. Cohen, G. Cudkowicz, andR. T. McCluskey (eds):Cellular Interactions in Immune Responses pp. 93–102, S.Karger, Basel, Switzerland, 1971Google Scholar
  6. Cudkowicz, G.: Genetic control of resistance to allogeneic and xenogeneic bone marrow grafts in mice.Transplant. Proc. 7: 155–159, 1975PubMedGoogle Scholar
  7. Cudkowicz, G. and Bennett, M.: Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated “responder” mice.J. Exp. Med. 134: 83–102, 1971PubMedGoogle Scholar
  8. Cudkowicz, G. and Lotzova, E.: Hemopoietic cell-defined compenents of the major histocompatibility complex of mice: Identification of responsive and unresponsive recipients for bone marrow transplants.Transplant. Proc. 5: 1399–1404, 1973PubMedGoogle Scholar
  9. Cudkowicz, G. and Stimpfling, J. H.: Deficient growth of C57BL marrow cells transplanted in F1 hybrid mice. Association with the histocompatibility-2 locus.Immunology 7: 291–306, 1964Google Scholar
  10. Cudkowicz, G. and Stimpfling, J. H.: Hybrid resistance controlled by H-2 region: Correction of data.Science 147: 1056, 1965PubMedGoogle Scholar
  11. Demant, P., Snell, G. D., Hess, M., Lemmonier, F., Néauport-Sautès, C., and Kourilsky, F.: Separate and polymorphic genes controlling two types of polypeptide chains bearing the H-2 private and public specificities.J. Immunogenet. 2: 263–271, 1975Google Scholar
  12. Déniant, P. and Néauport-Sautès, C.: TheH-2L locus and the system of H-2 specificities.Immunogenetics 7: 295–311, 1978Google Scholar
  13. Egorov, I. K.: a mutation of the histocompatibility-2 locus in the mouse.Genetika 3: 136–144, 1967 (in Russian, English summary)Google Scholar
  14. Egorov, I. K. and Blandova, Z. K.: Genetic control of H-2 alloantigens as inferred from analysis of mutations.Immunogenetics 1: 97–107, 1974Google Scholar
  15. Harmon, R. C., Clark, E. A., O'Toole, C., and Wicker, L. S.: Resistance ofH-2 heterozygous mice to parental tumors. I. Hybrid resistance and natural cytotoxicity to EL-4 are controlled by theH-2D-Hh-1 region.Immunogenetics 4: 601–607, 1977Google Scholar
  16. Hansen, T. H., Cullen, S. E., Melvold, R. W., Kohn, H. I., Flaherty, L., and Sachs, D.: Mutation in a new H-2 associated histocompatibility gene closely linked to H-2D.J. Exp. Med. 145: 1550–1558, 1977PubMedGoogle Scholar
  17. Hansen, T. H. and Levy, R. B.: Alloantigens determined by a second D region locus elicit a strong in vitro cytotoxic response.J. Immunol 120: 1836–1840, 1978PubMedGoogle Scholar
  18. Klein, J., Flaherty, L., VandeBerg, J. L., and Shreffler, D. C.:H-2 haplotypes, genes, regions and antigens: First listing.Immunogenetics 6: 489–512, 1978Google Scholar
  19. Kohn, H. I., Klein, J., Melvold, R. W., Nathenson, S. G., Pious, D., and Shreffler, D. C.: The firstH-2 mutant workshop.Immunogenetics 7: 279–294, 1978Google Scholar
  20. Lemmonier, F., Néauport-Sautès, C., Kourilsky, F., and Démant, P.: Relationships between private and public H-2 specificities on the cell surfaceImmunogenetics 2: 517–529, 1975Google Scholar
  21. Lotzova, E. and Cudkowicz, G.: Hybrid resistance to parental NZW bone marrow grafts.Transplantation 12: 130–138, 1971PubMedGoogle Scholar
  22. Lotzova, E. and Cudkowicz, G.: Hybrid resistance to parental WB/Re bone marrow grafts.Transplantation 13: 256–264, 1972PubMedGoogle Scholar
  23. Lotzova, E. and Cudkowicz, G.: Resistance of irradiated F1 hybrid and allogeneic mice to bone marrow grafts of NZB donors.J. Immunol. 110: 791–800, 1973PubMedGoogle Scholar
  24. McKenzie, I. F. C., Morgan, G. M., Melvold, R. W., and Kohn, H. I.: BALB/c-H-2 db a new H-2 mutant in BALBc/Kh that identifies a locus associated with the D region.Immunogenetics 4: 333–347, 1977Google Scholar
  25. Melvold, R. W. and Kohn, H. I.: Eight new histocompatibility mutations associated with theH-2 complex.Immunogenetics 3: 185–191, 1976Google Scholar
  26. Morgan, G. M., McKenzie, I. F. C., and Melvold, R. W.: The relationships between theH-2 loss mutations ofH-2 da andH-2 db in the mouse.Immunogenetics 7: 247–258, 1978Google Scholar
  27. Nakamura, I., Nakano, K., and Cudkowicz, G.: F1 hybrid anti-parent H-2d cytotoxicity: genetic control by H-2D and H-2L genes.In XIIIth International Leukocyte Culture Conference, National Research Council of Canada, in press, 1979Google Scholar
  28. Shearer, G. M. and Cudcowicz, G. Induction of F1 hybrid anti-parent cytotoxic effector cells: anin vitro model for hemopoietic histocompatibility.Science 190: 890–893, 1975PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Michael Bennett
    • 1
  • Roger W. Melvold
    • 2
    • 3
  • Henry I. Kohn
    • 3
  1. 1.Department of PathologyBoston University School of MedicineBoston
  2. 2.Section of Medical Oncology, Departments of Medicine and Microbiology-Immunology and the Cancer CenterNorthwestern University Medical SchoolChicago
  3. 3.Department of Radiation Therapy, Harvard Medical School and Shields Warren Radiation LaboratoryNew England Deaconess HospitalBoston

Personalised recommendations