Heterogeneity of the Bone Marrow Plasma Cell Pool

骨髓浆细胞库的异质性

• 批准号: 8645408
• 负责人: Irene Chernova
• 金额: $ 2.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645408
• 关键词: Ablation; Affect; Affinity; Antibodies; Antibody Formation; Antigens; Autoimmune Diseases; B-Lymphocytes; Biological Models; Bone Marrow; Cell Communication; Cell Lineage; Cells; Characteristics; Data; Disease; Engineering; Generations; Genes; Heterogeneity; Immunization; Immunoglobulin Somatic Hypermutation; Infection; Kinetics; Life; Maintenance; Mediating; Medicine; Memory B-Lymphocyte; Mission; Modeling; National Heart, Lung, and Blood Institute; Plasma Cells; Play; Population; Receptors, Antigen, B-Cell; Regulation; Rheumatoid Arthritis; Role; Serum; Signal Transduction; Somatic Mutation; Specificity; Structure of germinal center of lymph node; T-Lymphocyte; TNFRSF5 gene; TNFSF5 gene; Testing; Therapeutic; Transfusion; Vaccine Antigen; Vaccine Design; base; defined contribution; design; experience; mouse model; programs; public health relevance; research study

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.

描述（由申请人提供）：维持分泌抗体细胞池和血清抗体滴度所需的信号仍然很差。该建议的重点是确定持续存在的抗原在维持血清抗体滴度中是否起关键作用。维持抗原特异性血清滴度需要持续抗原的主张对疫苗设计具有深远的影响，因为必须设计所有免疫抗原才能在体内形成终身仓库。为了通过抗原刺激的B细胞馈物群体消除BM PC池的播种，B细胞将被剥夺T细胞帮助，并将对记忆B细胞群体的B细胞受体进行实验修订，以免对抗原反应。如果发现BM PC池需要由馈线种群维护，则将证明需要持续的抗原维持保护性抗体滴度。总体而言，该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，从而履行NHLBI的输血医学和细胞疗法计划的任务。