Elements of B Cell Memory

描述（由申请人提供）：具有更大、更快和 重复免疫后更特异的抗体应答，免疫学 记忆仍然知之甚少，但被广泛操纵，以防止 疾病。拟议研究的总体目标是表征 从幼稚B细胞产生B细胞记忆应答的手段， 确定维持这种反应的要求。阐明本 的B细胞记忆的元素，在小鼠中产生了一种新的实验系统。 这些小鼠（单克隆B-T小鼠）具有敲入的重链基因， λ轻链和转基因T辅助T细胞受体。因为他们是 在V（D）J重组酶阴性背景中工程化的一抗， 库是单克隆的，并且可以响应免疫而多样化。在 这样，通过用半抗原-载体缀合物免疫， 并且产生存储器B单元。在小鼠模型的一个变体中， B细胞的免疫球蛋白表达将受到泰特阻遏物的调节 系统（诱导型免疫球蛋白小鼠）。在这些小鼠中， 记忆将研究在各种条件下的表面IG表达的 B细胞这些研究的一个目标是确定记忆B细胞是否在 除了浆细胞可以确定后，主要反应，以及是否 记忆B细胞具有活化或静止表型。另一个目标是 确定B细胞表面IG的表达是否会影响细胞 在被激活的细胞接合后，向效应-浆细胞相对于记忆细胞分化 抗原的这些目标将通过分析抗原特异性IG来实现 滴度和重链V外显子的体细胞超突变分析 在用同源抗原免疫之后。

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.