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overview B cells of the immune system produce antibodies, which bind and neutralize infectious pathogens such as viruses and bacteria. To generate a repertoire of approximately 10^11 antibodies that can recognize the various molecules produced by different pathogenic organisms, each B cell independently reorganizes its DNA in two stages. In the first stage, which occurs during their development, the B cells will produce an antibody molecule that can bind to a target molecule but is limited in its ability to mobilize other components of the immune system. In the second stage, which occurs when the mature B cell encounters a pathogenic organism, the B cells will modify the antibody to allow it to bind more tightly to the target molecule and to activate specific arms of the immune system. Our research studies are focused on studying the processes that promote the second stage of antibody diversification. We use molecular, biochemical, cellular, genetic, and immunological experiments to understand how the B cells modify the blueprint of the antibody they were assigned to generate during development. Although the primary function of the second stage of antibody diversification is to mount the most effective immune response, aberrant DNA reorganization during this stage can activate genes that can cause cancer, specifically B cell lymphomas. Thus, these studies are critical in understanding how we can manipulate antibody diversity to drive more effective immune responses and how specific molecular pathways are redirected towards permitting cancerous cell growth rather than immunity.
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