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 bearing the 16/6 idiotype (16/6 Id) or with a mouse monoclonal anti-idiotypic antibody specific for the 16/6 Id. Susceptibility to the induction of experimental SLE is genetically determined but is not linked to the MHC. In the present study we tested the susceptibility of BM chimeras of different donor-host combinations to the induction of SLE and found that high levels of anti-16/6 Id and anti-ssDNA antibodies were induced in BALB/c --> C57BL/6, BALB/c --> BALB/c and normal BALB/c mice as 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 C57BL/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 demonstrate that the production of SLE-related autoantibodies is controlled by donor-type BM derived cells and not by host-type cells in the thymic stroma.