Stimulation of murine lymphocytes with antigen or mitogen in vitro can lead to the production of macrophage migration inhibition factor (MIF). In this study, variations in MIF production were examined in various inbred strains of mice. When BALB/c (H-2d) and AKR (H-2k) splenic lymphocytes were cultured with concanavalin A (Con A) in serum-free medium, good MIF production resulted within 24 to 48 hr. C3H/He (H-2k) cells cultured under identical conditions produced low levels of MIF and DBA-2 (H-2d) and C57BL/6 (H-2b) cells made no MIF response. Interestingly, however, C57BL/6 cells could make a good MIF response when the cell cultures were supplemented with 2% fetal calf serum (FCS) or if FCS was added to the supernatants after incubation. A similar pattern was observed with the cultures stimulated with specific antigen. This pattern of reactivity demonstrates that variation in MIF production is not directly related to differences in the H-2 complex.
The ability of preformed MIF from one strain to react with target cells from different strains was also examined. It was found that MIF produced by Con A-stimulated lymphocytes of a given strain was capable of inhibiting the migration of allogeneic macrophages as effectively as macrophages from the MIF producing strain. Furthermore, immunoadsorption of MIF-active supernatants with alloantisera directed against H-2 regions failed to remove MIF activity. Taken together, these results suggest that MIF activity as well as production are not under direct H-2 control and that the MIF molecule does not share antigenic determinants coded by the murine major histocompatibility complex.