Plasma Cell Regulation by Purinergic Receptors

项目总结 分泌自身抗原抗体的浆细胞对人类构成相当大的威胁 人类健康。此外，由于许多浆细胞的寿命非常长， 需要策略来耗尽分泌致病物质的长寿命浆细胞(LLPC) 抗体。这个项目的中心假设是，骨髓中的LLPC产生 通过感知细胞外的ATP与特定的成员 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。为了检验我们的假设，我们将： 1)确定P2rX抑制剂对LLPC产生和维持的影响，以及2) 确定嘌呤能受体P2rX4在早期浆细胞诱导和分化中的作用 LLPC维护。这些研究将提供独特和必要的洞察 LLPC使用的专门生存机制。这项工作支持了我们长期的 制定有效和具体禁用或耗尽的战略的目标 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.