Understanding Survival of Human Bone Marrow Long-Lived Plasma Cells

 描述(申请人提供)：长寿浆细胞(LLPC)终生维持保护性抗体的产生，但几十年来我们一直无法确定人类LLPC的细胞来源。在我们的实验室中，我们已经明确地将长寿病毒血清抗体来源与人类骨髓(BM)内的单个细胞室联系起来。PC的特异性集中在这些独特的、长寿的病毒特异性上，这些特异性来自40-60年前的暴露。在这一应用中，我们将通过(1)了解短命PC和LLPC的个体发育和存活，(2)检测LLPC存活的内在分子机制，以及(3)确定LLPC独特的代谢特征，来研究LLPC的生存机制。这项工作的意义是多方面的，从理解人类LLPC的产生方式到维持(或生存)的机制。它将为设计疫苗佐剂、开发自身免疫、过敏和移植等疾病中致病浆细胞的新靶点(保护LLPC)提供见解，并提供治疗多发性骨髓瘤(肿瘤学)的新诊断测试和药物途径。

 DESCRIPTION (provided by applicant): Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime but the identity of the cellular source of human LLPC has eluded us for decades. In our lab, we have definitively linked the long-lived viral serum antibody source to a single cellular compartment within the human bone marrow (BM). The PC specificities concentrate in these unique long-lived viral specificities from exposures that occurred over 40-60 years ago. In this application, we will study the survival mechanisms of human BM LLPC by (1) understanding the ontogeny and survival of the short-lived PC and the LLPC, (2) testing the intrinsic molecular mechanisms of LLPC survival, and (3) defining the unique metabolic signatures of LLPC. The significance of this work is several-fold from understanding the means of generation to the mechanisms of maintenance (or survival) of human LLPC. It will provide insights to designing vaccine adjuvants, developing novel targets of pathogenic plasma cells in diseases such as autoimmunity, allergy, and transplantation (sparing protective LLPC), and offering novel diagnostic testing and drug pathways to treat multiple myeloma (oncology).