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. 1974 May 1;139(5):1093–1109. doi: 10.1084/jem.139.5.1093

MECHANISMS OF GENETIC RESISTANCE TO FRIEND VIRUS LEUKEMIA IN MICE

I. ROLE OF89Sr-SENSITIVE EFFECTOR CELLS RESPONSIBLE FOR REJECTION OF BONE MARROW ALLOGRAFTS

Vinay Kumar 1, Michael Bennett 1, Robert J Eckner 1
PMCID: PMC2139650  PMID: 4596510

Abstract

Resistance to malignant erythropoiesis induced by Friend spleen focus-forming virus and resistance to marrow stem cell allografts are under genetic control. Strains of mice, e.g., C57BL/6 and B10.D2, which are homozygous for resistance at the Fv-2 locus, are also good rejectors of most bone marrow allografts. 89Sr, a bone-seeking isotope, irradiates marrow but not other lymphoid organs and abrogates resistance to marrow allografts without suppressing T- or B-cell functions. Thus, marrow-dependent effector cells (M cells) seem to resist allogeneic stem cells. To test if the genetic resistance to Friend virus (FV) is also mediated by M cells, B6 mice were treated with 89Sr using a dosage schedule known to abrogate resistance to allogeneic marrow cells. 9 days after FV infection of such mice, the spleens showed malignant erythroblastosis which could not be suppressed by prior hypertransfusion, a procedure which suppresses physiologic erythropoiesis. Such 89Sr-treated B6 mice also supported extensive virus replication, while control mice did not. FV markedly suppressed the ability of 89Sr-treated B6 mice to produce antisheep red blood cell (SRBC) antibodies, a feature seen normally only in genetically susceptible mice. Thus, 89Sr-treated B6 mice behaved in these respects as if they were susceptible to FV. When increasing doses of 89Sr were administered to B6 mice, a dose-related loss of resistance to FV was seen. Therefore, it appears that 89Sr-sensitive M cells mediate the genetic resistance to FV. The results of experiments with 89Sr indicated that genetically resistant mice would be expected to possess target cells which are susceptible to transformation by FV. To verify this corollary, bone marrow cells from B10.D2 (Fv-2rr) mice were transplanted into previously infected and lethally irradiated DBA/2 (Fv-2ss) recipients which share the same H-2d alleles. 5–15 days later, the spleens of DBA/2 primary recipients yielded transformed cells which were capable of producing splenic tumor colonies upon transplantation into adult, unirradiated B10.D2 secondary recipients. Various control experiments clearly indicated that the tumor colonies so induced were of B10.D2 marrow origin. This indicated that B10.D2 stem cells could be transformed when allowed to interact with FV in the spleens of susceptible DBA/2 mice. However, 30 days after transplantation of B10.D2 bone marrow cells into DBA/2 recipients, no transformed cells were detected. Apparently, in the 30-day interval precursors in the B10.D2 marrow gave rise to mature M cells which resisted the leukemic process. Since M cells recognize hybrid or hemopoietic histocompatability antigens expressed on primitive normal and transformed hematopoietic cells, we suggest that M cells may exert surveillance by rejecting leukemic cells. Thus, marrow transplantation from genetically resistant donors may provide a new mode of treatment for leukemia, by providing precursors of M cells and other immunocompetent cell types.

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Selected References

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

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