Redox Regulation of the Transcription Factor Pax-5.

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B cells play key roles in the immune response, as they are capable of producing and secreting large amounts of antibodies specific to foreign invaders. The B cell-specific transcription factor Pax-5a plays essential roles during B cell development, cell proliferation, and activation. The Pax-5 gene produces a total of four different protein isoforms: Pax-5a, 5b, 5d, and 5e. Previous work shows that the Pax-5e protein can increase the activity of Pax-5a protein. To investigate the function of Pax-5e in vivo, transgenic mice have been generated which overexpress the Pax-5e protein in B cells. Preliminary data show that such mice have increased numbers of precursor B cells in their bone marrow, while the number of mature B cells of such mice in the spleen is abnormally low. Furthermore, B cells of these transgenic mice show spontaneous cell proliferation in primary cell cultures. This project explores mechanisms that change the cell growth characteristics of B cells and their precursors in Pax-5e-overexpressing mice, focusing on bone marrow and spleen B cells. The intellectual merit of this project includes an increased understanding of the role of Pax-5e in B cell growth. This work is expected to increase knowledge concerning activity of transcription factors that regulate the antibody response. Results will provide new insight into the molecular pathways that lead to normal B cell proliferation as well as elucidate possible causes of malignant B cell growth. Broader impacts of this research include the exposure and research training that will be provided to the students of The College of William and Mary. As the William and Mary biology department has no Ph.D. program, research effort and productivity is entirely based on work by undergraduates and Master's students supervised by their PI. Students have the opportunity to become independent researchers and may be co-authors on papers. The research will also be discussed during seminar courses, exposing "non-research" students to molecular immunology research. In addition, the research will be presented annually at a local elementary school as part of a career program ("Science is women's work") aimed to increase science interest in girls.