The goal of the proposed research is to delineate the repertoire of immunoglobulin genes expressed by the cells from patients with systemic lupus erythematosus (SLE) and the impact of somatic hyper-mutation and subsequent selection and compare it with the normal repertoire. In addition, the immunoglobulin genes used by the autoantibody binding B cells from patients with SLE will be analyzed. The hypothesis to be tested is that SLE patients express an abnormal repertoire biased toward the production of autoantibodies. In order to determine the expressed repertoire accurately, a technique has been devised to analyze the rearranged immunoglobulin gene productions of individual B cells. By applying this technology to human B cells, an estimate of the full extent of the immunoglobulin repertoire has begun to emerge. Since their involves amplification of genomic DNA, both productive and non-productive rearrangements can be detected. Therefore, potential biases in the repertoire that may be related to molecular mechanisms of clonal selection can be revealed by this analysis. The goal is to assess the expressed immunoglobulin repertoire in patients with active and quiescent SLE. This should provide new insight into the possibility that there is an abnormality in the immunoglobulin repertoire in individuals with this autoimmune disease.
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