TRANSCRIPTIONAL REGULATION OF ANTIBODY RESPONSES AND IMMUNITY

描述（由申请人提供）：存在针对许多病原体的有效疫苗。但是，合理的设计方法未能产生针对许多重要病原体的疫苗。重要的是，我们对产生长期和广泛保护性免疫的分子途径的理解是不完整的。使用一种新发现的分子，该应用程序旨在了解调节B细胞提供持久和交叉保护抗体反应能力的途径。我们已经发现转录因子Zbtb20是维持长寿命浆细胞所必需的，只有高亲和力克隆在免疫后持续存在。这些发现为我们提供了一个独特的机会：1)通过遗传互补实验确定调节浆细胞多样性和寿命的信号通路和生存途径；2)确定低亲和力和中等亲和力抗体在病毒交叉保护和自身免疫发病机制中的作用。

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.