Pre-B cell receptor assesses the quality of IgH chains and tunes the pre-B cell repertoire by delivering differential signals
Pre-B cell receptor assesses the quality of IgH chains and tunes the pre-B cell repertoire by delivering differential signals
复制标题
DOI：
10.4049/jimmunol.177.4.2242
复制
发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Kawano, Yohei;Yoshikawa, Soichiro;Karasuyama, Hajime
人们充分了解 B 细胞发育过程中 DNA 水平上如何产生各种 Ig H 链和 L 链（BCR 的组成部分）。然而，在组装到 BCR 之前，是否以及如何监控每个组件的质量并进行选择，仍然很大程度上未知。在这里，我们表明，前 B 细胞产生的 mu H 链显示出形成前 BCR 的广泛能力，前 BCR 由 mu H 和替代轻 (SL) 链组成，对 B 细胞发育至关重要。前 B 细胞表面前 BCR 表达水平有所不同，具体取决于其 mu H 链与 SL 链配对的能力。前B细胞的前BCR表达水平越高，其前BCR信号传导越强，并且它们增殖和分化得越好。因此，单个前B细胞的存活、增殖和分化程度主要由其mu H链的SL配对能力决定。此外，在组装到 BCR 之前，通过评估其在 BCR 前检查点处与 SL 链配对的能力，具有较高与 IgL 链组装潜力的 IgH 链似乎被积极选择和扩增。这些结果表明，前 BCR 评估 mu H 链的质量，并通过驱动具有较高质量 mu H 链的细胞的优先扩增和分化来调整前 B 细胞库。
It is well understood how a variety of Ig H and L chains, components of BCR, are generated in the DNA level during B cell development. However, it has remained largely unknown whether and how each component is monitored for its quality and selected before the assembly into the BCR. Here we show that mu H chains produced by pre-B cells display a wide spectrum of ability to form the pre-BCR, which is composed of mu H and surrogate light (SL) chains and is crucial for B cell development. The level of surface pre-BCR expression varies among pre-B cells, depending on the ability of their mu H chains to pair with SL chains. The higher the level of pre-BCR expression by pre-B cells, the stronger their pre-BCR signaling, and the better they proliferate and differentiate. Thus, the extent of survival, proliferation, and differentiation of individual pre-B cells is primarily determined by the SL-pairing ability of their mu H chains. Furthermore, IgH chains with higher potential to assemble with IgL chains appear to be positively selected and amplified through the assessment of their ability to pair with SL chains at the pre-BCR checkpoint before the assembly into the BCR. These results indicate that the pre-BCR assesses the quality of mu H chains and tunes the pre-B cell repertoire by driving the preferential expansion and differentiation of cells with the higher quality of mu H chains.