Autoantibody production is a major component of several autoimmune diseases including Systemic Lupus Erythematosus (SLE). Although a number of mechanisms for controlling autoantibody production have been elucidated in mice, it remains unclear how tolerance is broken in most autoimmune diseases, including SLE. We have recently demonstrated that mouse germinal center (GC) cells express recombinase-activating genes 1 and 2 (RAG1, and RAG2) and re-activate Ig gene V(D)J recombination. The germinal center is a selective environment wherein B cells that develop autoreactive receptors by new recombination may be deleted. However, new V(D)J recombination in mature B cells is not limited to the GC and is also found in Ly-1 peritoneal B cells, which have been implicated in autoantibody production in the mouse. To further characterize V(D)J recombination in mature B cells we have developed assays for human Ig heavy and light chain recombination signal sequence (RSS) breaks. Human GC B cells, like their murine counterparts, were found to rearrange Ig kappa light chain genes, and express RAG1, RAG2, terminal deoxynucleotidyl transferase (TdT), l-like, and V-preB genes. We would now like to determine whether there is ongoing V(D)J recombination in mature B cell in autoimmune diseases.
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