Elements of B Cell Memory

描述(由申请人提供)：具有更大、更快和 重复免疫后更具特异性的抗体反应，免疫学 记忆仍然知之甚少，但却被广泛地用于预防 疾病的威胁。拟议研究的总体目标是描述 从未成熟的B细胞产生B细胞记忆反应的手段 定义维护此类响应的要求。为了澄清 B细胞记忆的元素，一种新的小鼠实验系统产生了。 这些小鼠(克隆B-T小鼠)具有敲入的重链基因，一种转基因的 Lambda轻链和转基因T辅助T细胞受体。因为他们是 在V(D)J重组酶阴性背景下进行工程，一次抗体 曲目是单克隆性的，可以根据免疫情况而多样化。在……里面 这样，通过用半抗原-载体结合物免疫，记忆反应 并产生记忆B细胞。在小鼠模型的一个变种中， B细胞的免疫球蛋白表达将受tet抑制物的调节 系统(可诱导免疫球蛋白小鼠)。在这些小鼠中，B细胞的产生 在不同的表面免疫球蛋白表达条件下，记忆将被研究 B细胞。这些研究的一个目标是确定记忆中的B细胞 增加浆细胞可以确定后的初步反应和是否 记忆B细胞有激活或静止的表型。另一个目标是 确定B细胞表面表达Ig是否会影响细胞 诱导分化为效应浆细胞与记忆细胞 抗原。这些目标将通过分析抗原特异性Ig来实现 重链V外显子的滴度和体细胞超突变分析 在用同源抗原免疫后。

DESCRIPTION (provided by applicant): Characterized by a greater, faster and more specific antibody response alter repeated immunization, immunological memory is still poorly understood and yet widely manipulated for the prevention of disease. The overall goal of the proposed research is to characterize the means by which a B-cell memory response is generated from naive B-cells and to define the requirements for the maintenance of such responses. To elucidate the elements of B-cell memory, a novel experimental system in mice was generated. These mice (monoclonal B-T mice) have a knock-in heavy-chain gene, a transgenic lambda light chain and a transgenic T helper T-cell receptor. Because they are engineered in a V(D)J recombinase-negative background, the primary antibody repertoire is monoclonal and can be diversified in response to immunization. In this way, by immunization with a hapten-carrier conjugate, a memory response and memory B-cells are generated. In one variant of the mouse models, the immunoglobulin expression by the B-cells will be regulated by the tet repressor system (Inducible immunoglobulin mice). In these mice, generation of B-cells memory will be studied under various conditions of surface Ig expression by the B-cells. One goal of these studies is to determine whether memory B-cells in addition to plasma cells can be identified after a primary response and whether memory B-cells have an activated or resting phenotype. Another goal is to determine whether expression surface Ig on B-cells will affect cell differentiation to effector-plasma cell vs. memory cell upon engagement by antigen. These goals will be achieved by analysis of the antigen specific Ig titer and by analysis of somatic hypermutation of the heavy-chain V exons following immunization with the cognate antigen.