Cellular site and mode of Fv-2 gene action. II. Conditional protection of Fv-2ss cells by admixture with Fv-2rr cells

Abstract

Fv-2ss marrow cells are protected in vivo from Friend virus-induced erythroleukemia by admixture with a preponderance of Fv-2rr marrow cells. This was demonstrated both in allophenic (mosaic) mice and in bone marrow chimeras constructed from C57BL/6 strains differing at Fv-2 and an enzyme marker (glucose phosphate isomerase). The bone marrow chimeras were constructed by injection of marrow cells from Fv-2ss mice into unirradiated Fv-2rr mice. Bone marrow chimeras derived from this procedure produced 1%-2% donor (Fv-2ss) erythrocytes; this level of chimerism was maintained indefinitely. All the bone marrow chimeras as well as allophenic mice with less than 20% Fv-2ss red cells failed to develop any of the symptoms of Friend disease after infection with the polycythemic strain of Friend virus. The Fv-2rr-mediated protection of Fv-2ss marrow cells could be reversed by pretreatment of the two types of chimeras with either monoclonal or polyclonal antithymocyte antisera. Chimeras treated with either reagent and infected with Friend virus developed symptoms of Friend disease and experienced a shift in their erythrocyte mosaic composition favoring cells of the susceptible genotype. These results are consistent with the notion that a functioning immune system plays a role in the Fv-2rr-mediated protection of Fv-2ss Friend virus target cells. Furthermore, these studies establish conditions whereby a small population of sensitive strain cells in an overwhelming background of resistant strain cells can be selectively expanded. Such conditions could be useful in efforts to clone the Fv-2 gene.