Natural resistance of irradiated 129-strain mice to bone marrow allografts: Genetic control by theH-2K region |
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Authors: | Gustavo Cudkowicz John F Warner |
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Institution: | (1) Departments of Pathology and Microbiology, School of Medicine, State University of New York at Buffalo, 14214 Buffalo, New York |
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Abstract: | A major genetic determinant of natural resistance to bone marrow allografts, designated asHh-3, was mapped to theH-2K region. This gene may code for or regulate the expression of cell surface structures selectively expressed on donor hemopoietic cells and recognized by naturally occurring cytotoxic effectors. Resistance was observed as failure of donor cell growth in the spleen of irradiated 129-strain (H-2
bc
) recipients of H-2k bone marrow cells. The mapping was accomplished by substituting donor cells bearingk alleles throughout theH-2 complex with cells of recombinant mouse lines bearingk alleles at definedH-2 regions. The host antigraft reaction underlying resistance was abrogated by pretreating 129-strain mice with either rabbit antimouse lymphocyte serum or the antimacrophage agent silica. Grafting of H-2Kk cells into mice ancestrally unrelated to 129 but sharing theH-2
bc
or the similarH-2
b
haplotype, and intoH-2
b/k
,H-2
k/bc
, andH-2
k/d
F1 hybrids revealed that resistance was unique to 129 mice, since mice of the other strains, including F1 hybrids, were susceptible to the grafts. Thus,Hh-3 incompatibility was a necessary but insufficient condition for the manifestation of allogeneic resistance; other genetic factors not associated withH-2 conferred responder status to 129-strain mice and nonresponder status to D1.LP, B10.129(6M), B10, B6, and possibly to F1 hybrid mice. The possible relationships between allogeneic resistance to H-2k marrow grafts, hybrid resistance to H-2k lymphomas, and F1 hybrid antiparental H-2k cytotoxicity induced in vitro are discussed. |
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Keywords: | |
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