ANTIGEN RECOGNITION AND ACTIVATION OF IMMUNOCOMPETENT CELLS

免疫活性细胞的抗原识别和激活

• 批准号: 3821938
• 负责人: W E PAUL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/3821938
• 关键词: B lymphocyte; antibody formation; antigens; calcium metabolism; crosslink; electrophoresis; genetic regulation; histocompatibility gene; immunogenetics; immunoglobulin genes; immunoglobulins; immunoregulation; inositol phosphates; interferons; leukocyte activation /transformation; lymphoma; neoplastic cell; phorbols

Cross-linkage of membrane immunoglobulin (Ig) on resting B lymphocytes leads to cellular activation. Biochemical correlates of this cellular activation that have been identified are rapid accumulation of inositol-1,4,5 trisphosphate, rapid increase in cytosolic free calcium concentration (Ca2+)i and striking enhancement in protein kinase C (PKC)-mediated protein phosphorylation. These early biochemical events appear to be important in B cell activation because mimicking them with pharmacologic agents causes B cell activation. We have recently demonstrated that phorbol myristate acetate treatment of B cells blocks signalling normally generated by receptor cross-linkage. Such cells fail to show increased inositol phospholipid metabolism or to elevate (Ca2+)i, indicating that their receptors have been desensitized. These cells are not activated as a result of receptor-cross linkage, providing further support for the importance of these biochemical events in cellular activation. Studies of the substrates of PKC revealed that one of the principal proteins phosphorylated by PMA-treatment of resting B cells was the nuclear intermediate filament protein lamin B. The rapid phosphorylation of a nuclear protein by PMA and by receptor cross-linkage suggests a mechanism through which receptor mediated signals may be communicated to the nucleus. The structural basis of signalling is being studied through the creation of chimeric genes involving exons of class I major histocompatibility complex genes and of Ig genes. These genes have been transferred into B lymphomas and have been shown to be expressed under the influence of interferon. Studies of the capacity of these chimeric membrane proteins to signal upon cross-linkage are now in progress.

静止B上膜免疫球蛋白（Ig）的交联 淋巴细胞导致细胞活化。 生化相关 已经鉴定出的这种细胞激活很快 肌醇1,4,5三磷酸的积累，快速增加 胞质游离钙浓度（Ca2+）I和醒目 蛋白激酶C（PKC）介导的蛋白的增强 磷酸化。 这些早期的生化事件似乎是 在B细胞激活中很重要，因为模仿它们 药理剂会导致B细胞激活。 我们最近有 证明了佛罗宝石对B细胞的醋酸肉豆蔻酸酯治疗 块通常由受体交叉链接产生的信号传导。 这些细胞未能显示出增加的肌醇磷脂代谢增加 或提升（Ca2+）i，表明它们的受体已经 脱敏。 这些单元没有因 受体交叉链接，为 这些生化事件在细胞激活中的重要性。 对PKC底物的研究表明，其中一项 主蛋白通过静息B的PMA处理磷酸化 细胞是核中间细丝蛋白层粘连蛋白B。 PMA对核蛋白的快速磷酸化和 受体交叉链接提出了一种机制 受体介导的信号可以传达给核。 信号的结构基础正在通过 创建涉及I级外显子的嵌合基因 组织相容性复合基因和Ig基因。 这些基因 已转移到B淋巴瘤中，已被证明 在干扰素的影响下表达。 研究 这些嵌合膜蛋白的能力发出信号 交叉链接正在进行中。