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overview Dr. Linda Spatz is interested in understanding how anti-double stranded (anti-dsDNA) antibodies which are the hallmark of the autoimmune disease Systemic Lupus Erythematosus (SLE), arise. Her laboratory is studying the regulation of anti-dsDNA B-cells. Normally these B cells are kept from secreting transgenic anti-ds DNA antibodies by regulatory mechanisms, collectively known as B cell tolerance. When one or more of these regulatory mechanisms goes awry, a breakdown in tolerance ensues and anti-dsDNA antibodies are secreted at elevated levels. These antibodies can deposit in various organs of the body including the skin, joints, and kidney where they can induce tissue damage. Dr. Spatz's laboratory is investigating potential genetic and environmental factors that can lead to a breakdown in anti-dsDNA B cell tolerance. Using an anti-dsDNA transgenic mouse model she is currently studying how the overexpression of a B cell survival factor known as BAFF, can lead to the loss of B cell tolerance and the secretion of transgenic anti-dsDNA antibodies. In addition, Dr. Spatz is working in collaboration with Dr. Paul Gottlieb to study the role of the Epstein Barr virus (EBV) in the etiology of SLE. They have observed that immunization of mice with a major nuclear protein of EBV known as EBNA-1 can elicit the production of pathogenic anti-dsDNA antibodies that can deposit in the kidney. Future studies are addressing the mechanism by which EBNA-1 can elicit these anti-dsDNA antibodies.
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