SYSTEMIC LUPUS ERYTHEMATOSUS-RELATED AUTOANTIBODY PRODUCTION IN MICE IS DETERMINED BY BONE-MARROW-DERIVED CELLS

Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with either a human monoclonal anti-DNA antibody bear ing the 16/6 idiotype (16/6 Id) or with a mouse monoclonal anti-idioty pic antibody specific for the 16/6 Id. Susceptibility to the induction of experimental SLE is genetically determined but is not linked to th e MHC. In the present study we tested the susceptibility of BM chimera s of different donor-host combinations to the induction of SLE and fou nd that high levels of anti-16/6 Id and anti-ssDNA antibodies were ind uced in BALB/c --> C57BL/6, BALB/c --> BALB/c and normal BALB/c mice a s opposed to C57BL/6 --> BALB/c chimeras and normal C57BL/6 mice. The low levels of the anti-16/6 Id and anti-ssDNA antibodies produced by C 57BL/6 --> BALB/c chimeras immunized with the 16/6 Id did not reflect poor immune competence following fully allogeneic BMT as such chimeras were shown to produce high levels of antibodies to a T cell-dependent antigen (the synthetic polypeptide (Phe,G)-A- -L). These results demo nstrate that the production of SLE-related autoantibodies is controlle d by donor-type BM derived cells and not by host-type cells in the thy mic stroma.