Cooperation between lymphatic stroma and hematopoietic cells shapes protective immunity

 描述（由申请方提供）：我们的初步数据表明，抗原摄取依赖于LEC的扩增。如果淋巴结扩张导致抗原堆积，那么淋巴结收缩是否会导致抗原传递？抗原从LEC向造血来源的APC的传递/交换似乎有两种机制。首先，淋巴结的收缩导致LEC凋亡，因为淋巴结尺寸减小。可能是一些携带有果糖的淋巴细胞吸附了抗原。因此，通过凋亡LEC的摄取将存档的抗原给予树突细胞或其他抗原呈递细胞。第二种抗原交换机制发生在淋巴结恢复正常大小后。我们将讨论稳态抗原交换的机制，我们有初步的数据。我们将首先评估稳态下的抗原交换是否是补体介导的，其次评估稳态下的抗原交换是否是外来体介导的。我们的最后一个目标是测试多轮扩张和收缩如何影响抗原存档和抗原交换。抗原被存档的程度，即哪些LEC存档抗原，它在淋巴结扩张和收缩期间如何保留，以及它在多轮感染后如何保留和获得是该目标的焦点。我们的首要假设是淋巴结的扩张和收缩改变了LEC在感染或免疫过程中通过与造血来源的APC交换抗原而获得的抗原库。由于抗原交换导致的LEC上抗原保留的变化可能导致对再感染和延长免疫力的易感性的差异。

 DESCRIPTION (provided by applicant): Our preliminary data suggests that antigen uptake is dependent on the expansion of LECs. If expansion of the lymph node leads to antigen archiving, does contraction of the lymph node lead to antigen hand-off? There appear to be two mechanisms of antigen hand-off/exchange from LECs to hematopoietically derived APCs. First, contraction of the lymph node results in LEC apoptosis as the lymph node decreases in size. Presumably some of the LECs that apoptose are holding onto antigen. Thus, archived antigen is given to dendritic cells or other antigen presenting cells through the uptake of apoptotic LECs. A second mechanism of antigen exchange occurs after the lymph node has returned to normal size. We will address mechanisms of steady state antigen exchange for which we have preliminary data. We will first evaluate if antigen exchange in the steady state is complement mediated and second evaluate if antigen exchange in the steady state is exosome mediated. Our last aim will test how multiple rounds of expansion and contraction affects antigen archiving and antigen exchange. The extent with which antigen is archived, i.e. which LECs archive antigen, how it is retained during lymph node expansion and contraction, and how it is retained and acquired after multiple rounds of infection is the focus of this aim. Our overarching hypothesis is that expansion and contraction of the lymph node changes the library of antigens that LECs acquire during infections or immunizations by exchanging antigen with hematopoietically derived APCs. The resulting changes in antigen retention on LECs as a result of antigen exchange likely leads to differences in susceptibility to re-infection and prolonged immunity.