Spleen cells from BALB/c and C57BL/6 mice were tested for their reactivity against reciprocal hybrid tissues ((BALB/c x C57BL/6) F1 and (C57BL/6 x BALB/c) F1) in three assay systems: the mixed lymphocyte reaction (MLR); the Simonsen spleen-weight graft-vs.-host (GVH) assay; and a GVH mortality assay. It was shown that both F1's serve as equally effective stimulators of parental cells in the MLR. In the spleen-weight assay, BALB/c and C57BL/6 cells were equally active in a given host, but greater splenomegaly was observed in (BALB/c x C57BL/6) F1 hosts regardless of the donor strain. By contrast, BALB/c cells were much less lethal than C57BL/6 cells in (BALB/c x C57BL/6) F1 hosts than in (C57BL/6 x BALB/c) F1 hosts, and to a lesser degree C57BL/6 cells were less lethal than BALB/c cells in (C57BL/6 x BALB/c) F1 hosts. The possibility that modifying substances may differentially alter reactivity of parental lymphocytes and that considerations other than genotype determine the outcome of a GVH reaction are discussed in detail.

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