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Our laboratory is studying how antibody-forming cells respond to antigen by undergoing somatic hypermutation and class switch recombination so that they can produce higher affinity antibodies with more useful effector functions. The molecular and biochemical mechanisms of antibody variable region hypermutation and class switch recombination is being studied in mice that have mutations in various repair proteins in collaboration with Dr. Winfried Edelmann. In order to examine detailed molecular mechanisms, we are also studying how mutation is targeted to antibody genes and some oncogenes in human Burkitt’s lymphoma cell lines which are undergoing variable region mutation in culture. These cell lines and genetically defective mice are being used to study the role of activation induced deaminase (AID), mismatch repair and error prone polymerases in the variable region hypermutation and isotype switching. The analysis of these events also involves the examination of AID activity biochemically and, in collaboration with Drs, Aviv Bergman and Thomas MacCarthy, computationally to analyze and simulate the details of the mutational activity that leads to the generation of antibody diversity.
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Shanzhi Wang, Kyeryoung Lee,Stephen Gray,Yongwei Zhang,Catherine Tang, Rikke B. Morrish,Elena Tosti,Johanna van Oers,Paula E. Cohen,Thomas MacCarthy,Sergio Roa,Matthew Scharff,
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