Heterogeneity of the Bone Marrow Plasma Cell Pool

描述（由申请人提供）：维持抗体分泌浆细胞池和血清抗体滴度所需的信号仍然不明确。本建议的重点是明确确定持久抗原是否在维持血清抗体滴度中起关键作用。维持抗原特异性血清滴度需要抗原的持久性，这一命题对疫苗设计具有深远的影响，因为所有免疫抗原都必须经过改造，在体内形成终身储存库。为了消除抗原刺激的B细胞饲养群体对BM PC池的播种，B细胞将被剥夺T细胞的帮助，记忆B细胞群体的B细胞受体将被实验性地修改，使其对抗原不产生反应。如果发现BM - PC池需要饲养种群来维持，这将证明需要持久抗原来维持保护性抗体滴度。总的来说，本提案中的实验将有助于更好地定义血清抗体维持的要求，并可能提出优化这些滴度的新方法，从而实现NHLBI输血医学和细胞治疗学项目的使命。

DESCRIPTION (provided by applicant): The signals required to maintain antibody-secreting plasma cell pools and serum antibody titers remain poorly defined. This proposal is focused on definitively determining whether persisting antigen plays a key role in maintaining serum antibody titers. The proposition that maintenance of antigen-specific serum titers requires persistence of antigen would have profound implications for vaccine design as all immunizing antigens would have to be engineered to form a lifelong depot in the body. To eliminate the seeding of the BM PC pool by antigen-stimulated B cell feeder populations, B cells will be deprived of T cell help and the B cell receptor of the memory B cell population will be experimentally revised so as to not be responsive to antigen. If it is found that the BM PC pool needs to be maintained by feeder populations it will be a demonstration of the need for persistent antigen for the maintenance of protective antibody titers. Overall, the experiments within this proposal will serve to better define the requirements for serum antibody maintenance and may suggest new ways to optimize these titers, thereby fulfilling the mission of the Transfusion Medicine and Cellular Therapeutics Program of the NHLBI.