Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis.
Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis.
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B淋巴细胞抗原受体的配体非依赖性信号传导及其在B淋巴细胞中阳性选择中的作用。
DOI：
10.1084/jem.194.11.1583
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发表时间：
2001-12-03
影响因子：
15.3
通讯作者：
Monroe, J G
中科院分区：
文献类型：
--
作者：
Bannish, G;Fuentes-Panana, E M;Cambier, J C;Pear, W S;Monroe, J G
通过B细胞抗原受体(BCR)的信号转导由正负调节因子的平衡决定。这种平衡被与细胞外配体结合而导致的聚集所改变。Bcr的聚集是表达bcr的B细胞诱导负选择或激活所必需的。然而，通过中间和成熟形式的BCR调节B细胞发育和外周内环境平衡的非配体信号已被假定。为了阐明非配体依赖的bcr信号功能及其调控在B细胞发育中的重要性，我们设计了一个模型，该模型允许我们将免疫球蛋白(Ig)α/含Igβ的bcr复合体的基本信号功能与依赖于配体介导的聚集的信号功能分离。在体内，我们发现基础信号足以促进前B-→前B细胞的转变，并产生未成熟/成熟的外周B细胞。产生基本信号和推动发育进程的能力都依赖于Igα/Igβ复合体的质膜结合和完整的免疫调节酪氨酸激活基序，从而建立了这些过程之间的相关性。我们认为，这些研究是第一次直接证明生物相关的基础信号通过BCR，在这种情况下，与常规和非常规细胞外配体相互作用的能力被消除。
Signal transduction through the B cell antigen receptor (BCR) is determined by a balance of positive and negative regulators. This balance is shifted by aggregation that results from binding to extracellular ligand. Aggregation of the BCR is necessary for eliciting negative selection or activation by BCR-expressing B cells. However, ligand-independent signaling through intermediate and mature forms of the BCR has been postulated to regulate B cell development and peripheral homeostasis. To address the importance of ligand-independent BCR signaling functions and their regulation during B cell development, we have designed a model that allows us to isolate the basal signaling functions of immunoglobulin (Ig)α/Igβ-containing BCR complexes from those that are dependent upon ligand-mediated aggregation. In vivo, we find that basal signaling is sufficient to facilitate pro-B → pre-B cell transition and to generate immature/mature peripheral B cells. The ability to generate basal signals and to drive developmental progression were both dependent on plasma membrane association of Igα/Igβ complexes and intact immunoregulatory tyrosine activation motifs (ITAM), thereby establishing a correlation between these processes. We believe that these studies are the first to directly demonstrate biologically relevant basal signaling through the BCR where the ability to interact with both conventional as well as nonconventional extracellular ligands is eliminated.