MURINE MODEL OF CUTANEOUS LYMPHOID HYPERPLASIA

皮肤淋巴组织增生(CLH)是一种慢性炎症反应 对外来抗原，如节肢动物的叮咬。尽管密度的大小 淋巴组织的浸润可以变化，在其最鲜艳的形式CLH是 以皮肤中淋巴组织的重新聚集为特征。我们的 研究表明，细胞组成和免疫构筑 人类CLH的特征与反应性淋巴组织的特征相似。 此外，我们已经证明，人类CLH代表着良性的 皮肤B-淋巴细胞增生性疾病的连续体 细胞淋巴瘤(CBCL)处于恶性的极端状态。中间人 我们首先发现了一种称为“克隆性CLH”的疾病。 成为一种能够最终在公开的CBCL中出现的过渡状态。 大约20年前，一种慢性淋巴细胞性肝炎的小鼠模型在 昆虫毒液的毒理学研究。我们的初步数据 论证了复制这一模式的可行性。在这 建议，我们的主要目标是完善这个小鼠CLH模型和 确定它是否可以驱动到克隆性CLH或CBCL。我们会 描述它的组织病理学，免疫结构特征， 克隆性与T细胞受体和免疫球蛋白基因V区 剧目。这将构成后续申请的基础 旨在识别抗原和MHC的长期资金 与CLH反应相关的限制因素及CLH发病机制 和CBCL，抑制CLH和CBCL的化学预防。因为 淋巴样增生-淋巴瘤连续体存在于许多器官系统 除了皮肤，对CLH-CBCL光谱的分析可能不仅仅是 为了提高我们对这些皮肤病的认识，也为了改善我们的 理解反应性和反应性之间的一般关系 其他器官系统中的肿瘤性B细胞疾病。我们也将从中获益 淋巴组织个体发育的新见解。这个项目是一个 与我们之前资助的工作显著背道而驰，因为它处理 与非人类疾病和特定动物模型的创建。在……里面 此外，它主要关注B细胞疾病，而我们之前的重点是 主要集中在T细胞疾病上。因此，它需要一个重大的 对研究工作进行重新定向和重组。

Cutaneous lymphoid hyperplasia (CLH) is a chronic inflammatory response to foreign antigens such as arthropod stings. Although the density of lymphoid infiltration can vary, in its most florid form CLH is characterized by a recapitulation of lymphoid tissue in the skin. Our studies have shown that the cellular composition and immunoarchitectural features of human CLH mimic those of reactive lymphoid tissues. Furthermore, we have shown that human CLH represents the benign end of a continuum of B-cell lymphoproliferative disorders with cutaneous B- cell lymphoma (CBCL) at its malignant extreme. An intermediate condition known as "clonal CLH" was first recognized by us and was shown to be a transitional state capable of eventuating in overt CBCL. Approximately 20 years ago, a murine model of CLH was identified during toxicological studies of insect venoms. Our preliminary data demonstrate the feasibility of reproducing this model. In this proposal, our principal aims are to refine this murine CLH model and determine if it can be driven to clonal CLH or CBCL. We will characterize its histopathology, immunoarchitectural features, clonality, and T-cell receptor and immunoglobulin gene V-region repertoires. This will form the basis of a subsequent application for long-term funding aimed at the identification of antigens and MHC restriction relevant to the CLH response, pathogenetic mechanisms of CLH and CBCL, inhibition of CLH and chemoprevention of CBCL. Because the lymphoid hyperplasia-lymphoma continuum exists in many organ systems besides the skin, analysis of the CLH-CBCL spectrum is likely not only to advance our knowledge of these skin diseases but also to improve our understanding of the general relationship between reactive and neoplastic B-cell disorders in other organ systems. We will also gain new insights into lymphoid tissue ontogeny. This project is a significant departure from our previously funded work because it deals with non-human disease and the creation of a specific animal model. In addition, it focuses primarily on B-cell disease while our prior focus has been mainly on T-cell disease. Therefore, it necessitates a major redirection and retooling of research efforts.