T CELL REGULATION OF B CELL ACTIVATION

T 细胞对 B 细胞激活的调节

• 批准号: 3813464
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813464
• 关键词: B lymphocyte; CD4 molecule; T cell receptor; T lymphocyte; antibody formation; antireceptor antibody; cell growth regulation; clone cells; extracellular matrix; granule; helper T lymphocyte; immunoglobulin G; immunoglobulin idiotypes; immunoregulation; interleukin 4; interleukin 5; leukocyte activation /transformation; major histocompatibility complex; monoclonal antibody

Supernatants of activated cloned T helper cells are capable of replacing T cells in the antigen specific and MHC restricted induction of B cell IgG antibody responses. Two distinct and synergizing activities were identified in this supernatant: Interleukin 4 and an antigen-specific and MHC-restricted factor. This latter factor can be affinity purified employing monoclonal antibodies specific for T cell receptor Vbeta8 determinants. Metabolic labeling and immunoprecipitation with anti-Vbeta8 antibody allowed detection in cell-free helper clone supernatants of a disulfide-linked dimer indistinguishable from the T cellsurface alpha-beta heterodimer. Biochemical analysis demonstrated that the cell-free alpha- beta heterodimer is indistinguishable from the cell-derived form. The cell free alpha-beta heterodimer is selectively associated with components of the CD3/T cell receptor complex in a detergent sensitive and apparently lipid membrane dependent state. The supernatants of activated type 2 T helper cell clone are capable of inducing polyclonal proliferation and immunoglobulin (Ig) secretion by heterogenous unprimed B cell populations. Studies employing recombinant lymphokines have demonstrated that IL5 is sufficient to induce these responses. Recombinant IL5 stimulation results in the appearance of a phenotypically novel B cell population which expresses high densities of Pgp-l (CD44) and relatively low densities of B220 (CD45) and Ia. Cell fractionation experiments demonstrate that the B cell subpopulation expressing this novel phenotype mediates nearly all of the proliferative and immunoglobulin secretory activity of the activated B cell populations. In addition, the Pgp-l expressed by these cells is capable of mediating binding to the extracellular matrix material hyaluronic acid, indicating a potential role for Pgp-l in regulating the trafficking of activated B cells in vivo.

活化的克隆T辅助细胞的上清液能够替代T细胞， 细胞中抗原特异性和MHC限制性诱导的B细胞IgG 抗体反应。确定了两种不同的协同作用活动 在该上清液中：白细胞介素4和抗原特异性， MHC限制因子。后一种因子可以亲和纯化 使用对T细胞受体V β 8特异的单克隆抗体 决定因素抗V β 8的代谢标记和免疫沉淀 抗体允许在无细胞辅助克隆上清液中检测A 二硫键连接的二聚体与T细胞表面α-β难以区分 异二聚体。生物化学分析表明，无细胞的α- β异源二聚体与细胞衍生形式不可区分。细胞 游离的α-β异二聚体选择性地与 CD 3/T细胞受体复合物对洗涤剂敏感， 脂膜依赖状态。 活化的2型T辅助细胞克隆的上清液能够 诱导多克隆增殖和免疫球蛋白（IG）分泌， 异源未致敏的B细胞群。使用重组 淋巴因子已经证明IL 5足以诱导这些 应答重组IL 5刺激导致出现一种 表型新颖的B细胞群，其表达高密度的 Pgp-1（CD 44）和相对低密度的B220（CD 45）和Ia.细胞 分级分离实验表明，B细胞亚群 表达这种新的表型介导了几乎所有的增殖性 和活化的B细胞群的免疫球蛋白分泌活性。 此外，由这些细胞表达的Pgp-1能够介导 与细胞外基质材料透明质酸结合，表明 Pgp-1在调节活化B细胞运输中的潜在作用 in vivo.