Connections between signal transduction components and cellular responses initiated by antigen receptor on B lymphocytes.
Connections between signal transduction components and cellular responses initiated by antigen receptor on B lymphocytes.
复制标题
信号转导成分与 B 淋巴细胞上抗原受体启动的细胞反应之间的联系。
DOI：
10.1084/jem.182.4.903
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Uhr,JW
中科院分区：
文献类型：
--
作者：
Scheuermann,RH;Uhr,JW
细胞将环境信号转化为各种细胞反应，包括增殖、分化和死亡。在许多情况下，这些反应是通过细胞外配体和膜结合受体之间的特异性相互作用引发的，然后触发一系列生物化学事件，统称为信号转导。在第二信使的鉴定和信号蛋白之间相互作用的理解方面已经取得了很大进展。此外，可以观察到特定的生化信号事件和细胞反应之间的相关性;然而，更难以实现直接因果关系的证明。两个观察使这一分析复杂化。首先，配体与其受体的结合可在同一细胞内导致几种不同的反应，例如，生长特征、转录模式、粘附特性、细胞因子分泌谱等的变化。由配体-受体相互作用诱导的任何细胞内生物化学事件可能参与这些下游反应之一的信号传导，而不是其他反应、反应的子集或所有反应。第二，不同分化阶段的细胞对相同的配体-受体相互作用可以产生不同的反应，例如，在一种情况下是增殖，而在另一种情况下是凋亡。为了阐明不同的信号通路，重要的是要了解哪些生化变化引起特定的反应。这种见解可能允许合理开发新的治疗药物，可以改变这些信号通路的特定分支。例如，在某些情况下，使用改变B淋巴细胞的粘附性质而不影响其活化、增殖或分化反应的药剂可能是有利的。几个最近的出版物已经描述了定义信号传导组分和由抗原受体（BCP，.）对B淋巴细胞的影响。B细胞以几种方式对它们的BCIK的交联作出反应：（a）复制和终末分化成浆细胞;（B）复制和分化成记忆细胞，然后在细胞周期中停滞;和（c）由于无反应性的诱导而对自身抗原产生耐受性
C ells translate environmental cues into various cellular responses, including proliferation, differentiation, and death. In many cases, these responses are initiated through a specific interaction between an extracellular ligand and a membrane-bound receptor, which then triggers a series of biochemical events collectively termed signal transduction. Much progress has been made in the identification of second messengers and understanding the interactions between signaling proteins. Moreover, correlations between specific biochemical signaling events and a cellular response can be observed; however, demonstration of a direct cause and effect relationship is more difficult to achieve. Two observations have complicated this analysis. First, the binding of a ligand to its receptor can result in several different responses within the same cell, eg, changes in growth characteristics, transcription patterns, adhesion properties, cytokine secretion profiles, et cetera. Any intracellular biochemical event induced by the ligand-receptor interaction might be involved in signaling one of these downstream responses and not the others, a subset of responses, or all of the responses. Second, cells of different differentiative stages can give different responses to the same ligand-receptor interaction, eg, proliferation in one case and apoptosis in another.To elucidate the different signaling pathways, it is important to understand which biochemical changes give rise to particular responses. Such insights may allow the rational development of new therapeutic agents that could alter particular branches of these signaling pathways. For example, under certain circumstances, it may be advantageous to use pharmaceutical agents that alter the adhesion properties of B lymphocytes without affecting their activation, proliferation, or differentiation responses. Several recent publications have described experiments that define connections between signaling components and specific downstream cellular responses initiated by engagement of the antigen receptor (BCP,.) on B lymphocytes. B cells respond to cross-linking of their BCIks in several ways:(a) replication and terminal differentiation into plasma cells;(b) replication and differentiation to memory cells that then become arrested in the cell cycle; and (c) tolerance to self-antigens as a result of the induction ofanergy