Autologous mixed lymphocyte reactions in NZB mice: analysis in recombinant inbred lines shows a T cell defect unrelated to autoantibody production.

The autologous mixed lymphocyte reaction (AMLR) has been examined in the AMLR-deficient strain, NZB, in C58 mice, which have normal AMLR responses, and in the (NZB x C58) recombinant inbred (NX8 RI) lines. Half of the NX8 RI lines had deficient AMLR and half were comparable in reactivity to the C58 parent strain. AMLR unresponsiveness did not correlate in the NX8 RI lines with H-2 or any other marker known to affect immune recognition. Non-T cells from H-2k NX8 RI lines which had deficient AMLR were able to stimulate an MLR when cultured with T cells of C58 origin. AMLR-positive H-2d lines responded to NZB stimulators, whereas NZB T cells did not respond to any of the H-2d NX8 RI lines but did exhibit strong alloreactivity. Thus, the AMLR defect in NZB mice is due to a T cell lesion. Furthermore, since AMLR deficiency in the NX8 RI lines did not correlate with a positive Coombs test or the production of naturally occurring thymocytotoxic antibody, we conclude that autoimmunity in NZB mice is a complex disease resulting from the inheritance of multiple independently segregating genes.