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：
10304171
负责人：
Deepta Bhattacharya
金额：
$ 46.05万
依托单位：
UNIVERSITY OF ARIZONA
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 2023-05-07
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10304171
关键词：
Adjuvant Aluminum Antibodies Antibody Diversity Antibody Formation Antibody Response Antibody-mediated protection Antigen Presentation Antigens B cell differentiation B-Cell Acute Lymphoblastic Leukemia B-Lymphocytes BTB/POZ Domain Binding Cell Count Cell Death Cell Survival Cell physiology ChIP-seq Chimera organism Chronic Data Dendritic Cells EMSA Event Family Fingers Genetic Genetic Transcription Goals Helper-Inducer T-Lymphocyte Humoral Immunities Immune response Immunity Immunization In Vitro Infection Inflammatory Length Ligands Lipid A Longevity Maintenance Measures Memory B-Lymphocyte Modeling Molecular Mus Myeloid Cells Physiological Plasma Cells Role Salts Signal Transduction Structure Structure of germinal center of lymph node System Testing Time Transcriptional Regulation Vaccinated Vaccination Vaccines Viral West Nile virus aluminum sulfate base cell type chronic infection cytokine experimental study genetic approach genetic corepressor in vivo mutant pathogen programs recruit response transcription factor

项目摘要

Abstract: The duration of antibody responses varies widely with the specific vaccine or infection. The specific features of the immunogen and host responses that are responsible for these differences remain poorly understood. In this application, we describe two transcription factors of the BTB/POZ family which exert opposing effects on the duration of antibody production. The first of these factors, Zbtb20, promotes plasma cell survival and is required for primary long-term antibody responses when aluminum salts, but not Toll-like receptor ligands are used as the adjuvant. The second factor, Zbtb32, promotes plasma cell death and limits the duration of antibody production following memory B cell recall responses, but not primary antibody responses. Based on these findings, we propose to establish the cellular events that explain how adjuvants influence the duration of immunity, and to uncover the physiological consequences to the diversity of antibody responses when recall responses persist for too long. Moreover, we propose to identify the molecular mechanisms of how Zbtb20 and Zbtb32 function to control the duration of humoral immunity.

摘要：抗体反应的持续时间随特定的疫苗或感染而变化很大。具体负责这些差异的免疫原和宿主反应的特征仍然很差理解。在此应用中，我们描述了BTB/POZ家族的两个转录因子对抗体产生持续时间的影响。这些因素中的第一个ZBTB20促进了等离子体细胞存活，对于铝盐而不是Toll-toll-toll-toll-toll-Toll-the Birime Respody抗体反应所必需受体配体用作佐剂。第二个因素ZBTB32促进了浆细胞死亡和极限记忆B细胞回忆反应后的抗体产生持续时间，而不是原代抗体回答。基于这些发现，我们建议建立细胞事件，以解释佐剂的方式影响免疫的持续时间，并发现对抗体多样性的生理后果召回响应持续时间太长时的响应。此外，我们建议鉴定分子 ZBTB20和ZBTB32如何控制体液免疫持续时间的机制。