Studies on Isoantigenic Variation in Mouse Lymphomas2

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Abstract
Studies on isoantigenic variation in lymphomas originating in homozygous and heterozygous F1 hybrid mice were made by serologic, chromosome cytologic, and transplantation tests. The homozygous lymphomas grew only in their genotype of origin, while the F1 lymphomas gave rise to progressively growing variant sublines, selectively compatible with one or the other of the parental strains. Serologic tests by the method of Gorer and O'Gorman showed that the variants had lost their sensitivity to cytotoxic antibodies directed against H-2 isoantigens derived from the opposite parental strain. This sensitivity could not be restored by serial passages of the variant subline in the F1 genotype of origin or in the opposite parental strain for 12 to 17 transfer generations. Homozygous lymphomas and the variants derived from heterozygous lymphomas were slightly more sensitive to the cytotoxic effect of H-2 isoantibodies than the F1 lymphomas were. It was not possible to select any isoantibody-resistant cells by 4 consecutive in vitro treatments of an F1 lymphoma, with antibodies directed against one of the parental strain components in the presence of complement. No chromosomal differences were found between the parental strain variants and the F1 tumors of origin in 2 cases examined. The permanence of the changes observed suggests that the mechanism of variant formation is genetic and possibly due to mitotic crossing over. However, epigenetic changes, possibly induced by antibodies directed against the foreign H-2 antigens during the period of background growth in the parental host, cannot be excluded.