REGULATION OF B CELL MEMORY

B 细胞记忆的调节

• 批准号: 6055445
• 负责人: JAN CERNY
• 金额: $ 24.91万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6055445
• 关键词: B lymphocyte; SCID mouse; antigen antibody reaction; bone marrow; cell differentiation; cell migration; cell sorting; clone cells; gene rearrangement; helper T lymphocyte; immunocytochemistry; immunologic memory; nucleic acid sequence; passive immunization; spleen

Memory B cells differentiate via a specialized pathway in the lymphoid germinal centers (GC) which is different from, and independent of the antibody formation and which includes somatic mutation and selections of cells with high affinity for the antigen. The regulation of the GC/memory pathway, which represents the most important adaptive immune mechanism, is poorly understood. This proposal will test three novel ideas about this regulation. One, it is postulated that GC/memory pathway of B cell differentiation is driven by specialized helper T cell (TH) subsets. These TH will be isolated by cell sorting and cellular cloning and their properties and mechanisms of action will be studied in vivo upon adoptive transfer into B cell-reconstituted scid mice immunized with hapten- carrier conjugates. The development of germinal centers (GC) in the spleen will be monitored by immunohistochemical techniques and the affinities of hapten-specific serum antibodies will be determined. The somatic hypermutation activity in the GC B cells will be studied by the sequence analysis of the rearranged VDJ segments that encode the H chains of hapten-specific Ab. Second, it is proposed that the GC/memory response may selectively stimulated with complexes of antigen (Ag) with antibody (Ab). This hypothesis will be tested using well-defined Ab of known isotype and affinity and the mechanism of the Ag/Ab complex activity in conjunction with the help provided by specific TH subsets and clones will be studied. Thirdly, it is proposed to determine whether the memory B cells home to bone marrow which appears to be a major site of the anamnestic Ab response and whether the bone marrow environment contribute to an additional molecular and functional maturation of the anamnestic antibody repertoire. The proposed studies will elucidate important mechanisms of immunological memory, provide tools for manipulation of the adaptive immune response and suggest novel strategies for vaccination.

记忆B细胞通过淋巴机中的专业途径区分 生发中心（GC）与不同的，独立于 抗体形成，其中包括躯体突变和选择 对抗原高亲和力的细胞。 GC/内存的调节 代表最重要的适应性免疫机制的途径， 理解很差。该建议将测试三个有关 这个法规。第一，假定B细胞的GC/内存途径 分化是由专门的辅助T细胞（Th）子集驱动的。 这些将通过细胞分选和细胞克隆及其 收养时，将在体内研究属性和作用机制 转移到B细胞重建的SCID小鼠中，用触觉免疫 载体缀合物。生发中心的发展（GC） 脾脏将通过免疫组织化学技术和 将确定触觉特异性血清抗体的亲和力。这 GC B细胞中的体细胞超数活性将由 编码H链的重排的VDJ段的序列分析 特定于Hahpten的AB。其次，建议GC/内存响应 可以用抗体的抗原（Ag）选择性刺激 （AB）。该假设将使用已知的明确定义的AB进行检验 同种型和亲和力以及Ag/Ab复合活动的机制 与特定子集和克隆提供的帮助相结合将 被研究。第三，建议确定内存B是否 骨髓中的细胞似乎是 厌食AB反应以及骨髓环境是否贡献 到达植物的额外分子和功能性成熟 抗体库。拟议的研究将阐明重要 免疫记忆的机制，提供了操纵的工具 适应性免疫反应并提出疫苗接种的新型策略。