VASCULAR-LESIONS IN MICE WITH A DEFICIT IN FAS-MEDIATED APOPTOSIS ANDTHEIR TRANSFER

The lpr and gld genes are thought to result in an incapacity for Fas-m ediated apoptosis of T and B cells and the development of subsequent a utoimmune disease. A newly established gld-congenic strain of mice, MR L/MpTn-gld/gld (MRL/gld), was found to develop vascular lesions involv ing arteritis and glomerulonephritis (GN), which were similar to those observed in the MRL/Mp-lpr/lpr (MRL/lpr) strain. However, comparative studies with a C3H/HeJ strain bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. We were success ful in transferring GN to normal MHC-compatible gld/gld and irradiated +/+ mice by bone marrow cells of MRL/gld mice, but were unsuccessful using those of C3H/gld mice. Transfer of arteritis, however, was only successful in mice with an MRL background. Nephritogenic monoclonal an tibodies obtained from an MRL/lpr and an MRL/gld mouse were shown to b e bone marrow-derived and rich in clonal diversity, and at least two o f these were capable of causing glomerular injury by different mechani sms. Development of GN and systemic arteritis in MRL/lpr and MRL/gld m ice will be dependent not only on their incapacity for Fas-mediated ap optosis but also on bone marrow cells and peripheral cells with intrin sic defects.