TRANSCRIPTIONAL REGULATION OF ANTIBODY RESPONSES AND IMMUNITY

抗体反应和免疫的转录调控

基本信息

批准号：
8901917
负责人：
Deepta Bhattacharya
金额：
$ 38万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-24 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901917
关键词：
1-Phosphatidylinositol 3-Kinase Affinity Animals Antibodies Antibody Affinity Antibody Diversity Antibody Response Antigens Apoptosis Autoimmune Process Autoimmunity Avidity B-Lymphocytes Cell Communication Chimera organism Data Gene Expression Genetic Goals Helper-Inducer T-Lymphocyte Immunity Immunization Infection Influenza Influenza vaccination Laboratories Length Life Longevity MEKs Maintenance Memory B-Lymphocyte Methods Modeling Molecular Mouse Strains Mus Noxae Pathogenesis Pathway interactions Peptides Physiological Plasma Cells Production Reaction Recombinants Recruitment Activity Relative (related person)Role Serum Signal Transduction Specificity Structure of germinal center of lymph node Testing Time Transcriptional Regulation Vaccination Vaccine Design Vaccines Variant Viral Virus West Nile virus base cross reactivity design genetic manipulation improved in vitro testing in vivo pathogen prevent research study transcription factor

项目摘要

DESCRIPTION (provided by applicant): Effective vaccines exist for many pathogens. But rational design methods have failed to generate vaccines against many important pathogens. Importantly, our understanding of the molecular pathways involved in generating long-lived and broadly protective immunity is incomplete. Using a newly discovered molecule, this application is directed at understanding pathways that regulate the ability of B cells to provide durable and cross-protective antibody responses. We have discovered that the transcription factor Zbtb20 is required for maintenance of long lived plasma cells, with only high affinity clones persisting afte immunization. These findings provide us with the unique opportunity to: 1) Identify the signaling and survival pathways that regulate plasma cell diversity and lifespan through genetic complementation experiments; 2) Determine the function of low and moderate affinity antibodies in cross-protection against viruses and in the pathogenesis of autoimmunity.

描述（由申请人提供）：许多病原体存在有效疫苗。但是，有理设计方法未能针对许多重要的病原体生成疫苗。重要的是，我们对产生长寿命和广泛保护性免疫涉及的分子途径的理解是不完整的。使用新发现的分子，该应用旨在理解调节B细胞提供持久和交叉保护抗体反应能力的途径。我们已经发现，维持长期存在的浆细胞需要转录因子ZBTB20，只有高亲和力克隆持续存在AFTE免疫。这些发现为我们提供了以下独特的机会：1）通过遗传互补实验确定调节血浆细胞多样性和寿命的信号传导和生存途径； 2）确定低和中等亲和抗体在针对病毒的交叉保护和自身免疫发病机理中的功能。