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Bone-marrow-cell grafts involving theH-2D andH-2L mutant haplotypes
Authors:Michael Bennett  Roger W Melvold  Henry I Kohn
Institution:(1) Department of Pathology, Boston University School of Medicine, 80 East Concord Street, 02118 Boston, Massachusetts;(2) Section of Medical Oncology, Departments of Medicine and Microbiology-Immunology and the Cancer Center, Northwestern University Medical School, 710 North Fairbanks Court, 60611 Chicago, Illinois;(3) Department of Radiation Therapy, Harvard Medical School and Shields Warren Radiation Laboratory, New England Deaconess Hospital, 50 Binney Street, 02115 Boston, Massachusetts
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 ldquohybrid resistancerdquo 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.
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