Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages

In addition, we now have been able to introduce the gene for susceptibility from the PRI mice into the C3H mice by the appropriate crosses and backcrosses and have established congenic lines of C3H, i.e., C3Hss (susceptible) and C3H (resistant), or in genetic terms, C3Hrr. It was the establishment of these two lines of mice which allowed us to differentiate between a hypothesis of conversion, presumed to be like that of transformation (7), and a change in susceptibility brought about by a mixed lymphocyte reaction. In 1962 when the original work on conversion was reported, there was little knowledge of lymphokines and their effect on macrophages. J. H. Huang, in unpublished experiments carried out in our laboratory in 1965, showed that increased susceptibility of resistant macrophage cultures was readily induced by the addition of "floating" cells (probably lymphocytes) to the fresh cultures of the resistant macrophages, which contained lymphocytes of another allogeneic type. It was supposed that the virus might be growing in the lymphocytes from the susceptible mice and attaining sufficient titer to destroy the macrophages. This hypothesis could not be ruled out until the congenic strains, C3H (C3Hrr) and C3Hss, had been established.