Decreased sensitivity of immunoselected and NK-selected YAC lymphoma sublines to hybrid resistance in vivo

Two sublines of the Moloney lymphoma YAC, selected by alternating in vitro exposure to anti-MCSA + complement and in vivo passage in preimmunized hosts, had a decreased or undetectable expression of MCSA. These 'immunoselected' sublines were compared with the original YAC line with regard to their ability to grow in a panel of semisyngeneic F₁ hybrids. Natural hybrid resistance to YAC, previously found to be mediated by NK cells, affected the immunoselected sublines to a much smaller extent. This was further corroborated by the fact that the same sublines showed a decreased sensitivity to the in vitro lysis by NK cells from the same hybrid genotypes. Another set of YAC variants were produced by repeated in vitro exposure to NK cells and intermittent passage in highly NK-active F₁ hosts. These 'NK-selected' sublines showed a permanently decreased sensitivity to NK lysis after 8-10 selections. When compared for in vivo growth with the parental YAC-1 tissue culture line in a spectrum of relatively resistant F₁ hybrids, they had an increased frequency of lakes. This is in line with recent findings which show a relationship between the target site for natural antibodies and anti-MCSA on the one hand, and between the natural antibody-binding site and the NK target site on the other.