Redox Regulation of the Transcription Factor Pax-5.

B细胞在免疫反应中起着关键作用，因为它们能够产生和分泌大量针对外来入侵者的特异性抗体。 B细胞特异性转录因子Pax-5a在B细胞发育、细胞增殖和活化过程中起重要作用。 Pax-5基因总共产生四种不同的蛋白质同种型：Pax-5a、5 b、5d和5e。 前期工作表明Pax-5e蛋白可以提高Pax-5a蛋白的活性。 为了研究Pax-5 e在体内的功能，已经产生了在B细胞中过表达Pax-5 e蛋白的转基因小鼠。 初步数据显示，这些小鼠的骨髓中前体B细胞的数量增加，而这些小鼠的脾脏中成熟B细胞的数量异常低。 此外，这些转基因小鼠的B细胞在原代细胞培养物中显示自发细胞增殖。 该项目探讨了Pax-5e过表达小鼠中B细胞及其前体细胞生长特性的变化机制，重点关注骨髓和脾脏B细胞。 该项目的智力价值包括增加对Pax-5 e在B细胞生长中的作用的理解。这项工作有望增加有关调节抗体反应的转录因子活性的知识。 结果将提供新的见解，导致正常B细胞增殖的分子途径，以及阐明恶性B细胞生长的可能原因。 这项研究的更广泛的影响包括将提供给威廉和玛丽学院的学生的曝光和研究培训。 因为威廉和玛丽生物系没有博士学位。计划，研究工作和生产力是完全基于工作的本科生和硕士生由他们的PI监督。 学生有机会成为独立的研究人员，并可能是论文的共同作者。 该研究也将在研讨会课程中进行讨论，使“非研究”学生接触分子免疫学研究。 此外，这项研究将每年在当地一所小学进行，作为旨在提高女孩对科学兴趣的职业方案（“科学是妇女的工作”）的一部分。

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.