Altered expression of Ly-49 receptors on NK cells developing in mixed allogeneic bone marrow chimeras

Ly-49 molecules are used by NK cells to distinguish 'self' from 'non-self', but the determinants of Ly-49 expression that allow this distinction to be made are not understood. The education of NK cells for self/non-self recog nition was studied In murine mixed allogeneic bone marrow chimeras, in whic h NK cells are of both host and donor origin. Marked alterations in Ly-49 r eceptor expression were observed on both host and donor NK cells developing in BALB/c --> B6 mixed chimeras. Ly-49A and Ly-49G2 expression was lower o n host B6 NK cells of mixed chimeras compared to non-transplanted B6 contro ls. Among donor BALB/c NK cells, Ly-49C expression levels were reduced, but the proportion of Ly-49C(+) cells was increased, whereas Ly-49G2 expressio n was up-regulated compared to non-transplanted BALB/c controls. Thus, Ly-4 9 expression on donor and host NK cells developing post-bone marrow transpl antation evolves toward the expression pattern of the host and donor strain s respectively due to the presence of the allogeneic MHC, In vitro function al NK cell assays showed that donor NK cells in mixed chimeras were not tol erant to host antigens and that host NK cells were not tolerant to the dono r. Our data are consistent with a model in which MHC expression in the envi ronment has a dominant down-regulating effect on the expression of Ly-49 mo lecules that recognize those MHC molecules, regardless of whether they are self or allogeneic. This down-regulation, combined with the limited reperto ire of Ly-49 molecules, may not be sufficient to allow NK cells to be toler ant of MHC antigens of a fully MHC-mismatched allogenic strain.