SELF-REACTIVE B-CELLS IN NONAUTOIMMUNE AND AUTOIMMUNE MICE

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for exa mple, is characterized by a discrete set of antibodies directed to nuc lear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE, The murine model of SLE, the MRL-lpr/lpr mouse, l ikewise, has a similar autoantibody profile. To understand how SLE-ass ociated autoantibodies are regulated in healthy individuals and to ide ntify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. T he development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of ant i-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.