Plasma Cell Regulation by Purinergic Receptors

项目摘要 分泌抗自身抗原的抗体的浆细胞对免疫系统构成相当大的威胁。 人体健康此外，由于许多浆细胞的寿命特别长， 需要策略来消耗分泌致病性毒素的长寿命浆细胞（LLPC）。 抗体的该项目的核心假设是骨髓中的LLPCs产生 细胞外ATP的特异性分子， 嘌呤能受体（P2rX）家族。因此，我们建议选择性地 毒物相关的嘌呤能受体将耗尽LLPC。为了验证我们的假设，我们将： 1)确定P2rX抑制剂对LLPC生成和维持的影响，以及2） 确定嘌呤能受体P2rX4在早期浆细胞诱导中的作用， LLPC维护。这些研究将提供独特的和必要的见解， LLPC使用的特殊生存机制。这项工作支持我们的长期 目标，以有效和具体地 有问题的浆细胞

Project summary Plasma cells that secrete antibodies against self-antigens pose a considerable threat to human health. Moreover, because many plasma cells are exceptionally long-lived, strategies are needed to deplete long-lived plasma cells (LLPCs) that secrete pathogenic antibodies. This project centers on the hypothesis that LLPCs in bone marrow generate requisite survival signals by sensing extracellular ATP with specific members of the purinergic receptor (P2rX) family. Hence, we propose that compounds that selectively poison relevant purinergic receptors will deplete LLPCs. To test our hypothesis, we will: 1) Establish the impact of P2rX inhibitors on LLPC generation and maintenance, and 2) Determine the role of the purinergic receptor P2rX4 in early plasma cell induction and LLPC maintenance. These studies will provide unique and needed insights into the specialized survival mechanisms employed by LLPCs. This work supports our long-term objective of developing strategies to effectively and specifically disable or deplete problematic plasma cells.