F1 hybrid resistance: long-term systemic effects sensitive to irradiation and age

In contrast to the usual rapid growth of transplanted syngeneic marrow cells in spleens of lethally irradiated recipients, the growth of parental marrow cells from certain inbred strains of mice is resisted by their F1 hybrids, other strains or both. The full complexity of this well known natural resistance is demonstrated here by using three inbred strains and their three F1 hybrids in all parent-hybrid combinations of donor and recipient. A similar resistance to parental marrow grafts is reported here in W-anemic F1 hybrid recipients that are cured and repopulated without irradiation. Rather than resistance to short-term growth in spleens, F1-hybrid resistance to permanent repopulation of the entire hemopoietic system is studied here. This manifestation of hybrid resistance is radiosensitive and declines in recipients over the age of 12 months. Long-term hemopoietic repopulation is measured quantitatively by injecting mixtures of two marrow-cell types with distinguishable hemoglobins into stem-cell-deficient recipients. A very high degree of resistance is detected against WB but not B6 parental marrow when mixed with WBB6F1 marrow and injected into WBB6F1 recipients. Most, but not all, of this resistance to permanent, systemic repopulation is abrogated by irradiation of the recipients; it is also abrogated after they reach the age of 15 months. Mouse models of long-term hybrid resistance studied in the entire hemopoietic system may be particularly relevant for marrow transplantation in man, where the objective is long-term systemic repopulation.