The pre‐B cell receptor and its ligands – it takes two to tango

The pre‐B cell receptor and its ligands – it takes two to tango
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前 B 细胞受体及其配体 – 需要两个人才能探戈

DOI:
10.1002/sita.200500055
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发表时间:
2007
期刊:
Signal Transduction
影响因子:
--
通讯作者:
Meister S.
Meister S.
中科院分区:
--
文献类型:
--
作者:
H. Vettermann;Meister S.

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早期前体B细胞的发育受表面结合的前B细胞受体控制,该受体由免疫球蛋白μ重链、替代轻链组分λ5和VpreB以及信号转导亚基免疫球蛋白α/免疫球蛋白β组成。前B细胞受体控制功能性B淋巴前体的克隆扩增、存活和有效分化;然而,来自该受体的信号如何启动仍存在争议。最近对Abelson鼠白血病病毒(Abl‐MuLV)转化的前B细胞系的研究表明,λ5的N末端非免疫球蛋白部分(所谓的独特尾)是通过介导前B细胞受体(前BCR)的自我聚集来启动细胞自主信号所必需的。然而,引人注目的是,λ5独特的尾部还控制着与两组不同的基质细胞来源的前BCR配体的相互作用,即硫酸乙酰肝素糖胺聚糖和表面相关半乳糖凝集素-1。尽管这些发现并不相互排斥,但它们刷新了关于前BCR信号启动的潜在模式的讨论。在这篇综述中,我们讨论了最近的关键发现,并提出了一个整合模型,在功能性B细胞前体的选择过程中,前BCR信号的配体依赖性和独立启动。
The development of early precursor B cells is governed by the surface‐bound pre‐B cell receptor consisting of the immunoglobulin μ heavy chain, the surrogate light chain components λ5 and VpreB, and the signal transducing subunits immunglobulin α/immunglobulin β. The pre‐B cell receptor controls clonal expansion, survival and efficient differentiation of functional B lymphoid precursors; however, it is still controversial how signals from this receptor are initiated. Recent studies with Abelson murine leukemia virus (Abl‐MuLV)‐transformed pre‐B cell lines suggest that the N‐terminal non‐immunoglobulin portion of λ5, the so‐called unique tail, is required to initiate cell‐autonomous signals by mediating self‐aggregation of the pre‐B cell receptor (pre‐BCR). Strikingly however, the λ5 unique tail also controls the interaction with two different groups of stroma cell‐derived pre‐BCR ligands, namely heparan sulfate glycosaminoglycans and surface‐associated galectin‐1. Even though these findings are not mutually exclusive, they refresh the discussion about potential modes of pre‐BCR signal initiation. In this review, we discuss recent key findings and propose an integrative model for ligand dependent and independent initiation of pre‐BCR signals during selection of functional B cell precursors.
VPREB1/VPREB2双缺陷小鼠中前体B细胞扩张的损失,但不是等位基因排除。
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