Understanding Survival of Human Bone Marrow Long-Lived Plasma Cells

 描述（由申请人提供）：长寿命浆细胞（LLPC）可在一生中维持保护性抗体的产生，但数十年来我们一直无法确定人LLPC的细胞来源。在我们的实验室中，我们已经明确地将长寿命的病毒血清抗体来源与人骨髓（BM）内的单个细胞区室联系起来。PC特异性集中在40-60年前暴露的这些独特的长寿命病毒特异性中。在本申请中，我们将通过（1）了解短寿命PC和LLPC的个体发育和存活，（2）测试LLPC存活的内在分子机制，以及（3）定义LLPC的独特代谢特征来研究人BM LLPC的存活机制。这项工作的意义是几倍，从了解人类LLPC的生成方式到维持（或存活）的机制。它将为设计疫苗佐剂提供见解，开发疾病中致病性浆细胞的新靶点，如自身免疫，过敏和移植（保留保护性LLPC），并提供新的诊断测试和药物途径来治疗多发性骨髓瘤（肿瘤学）。

 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).