Übelhart Rudolf, Werner Markus, Jumaa Hassan
Department of Immunology, Ulm University, 89081, Ulm, Germany.
Department of Molecular Immunology, Faculty of Biology, University of Freiburg, Freiburg im Breisgau, Germany.
Curr Top Microbiol Immunol. 2016;393:3-25. doi: 10.1007/82_2015_475.
During early stages of development, precursor B lymphocytes express a characteristic type of antigen receptor known as the pre-B-cell receptor (pre-BCR). This receptor differs from conventional BCRs in that it possesses a germ line-encoded surrogate light chain (SLC), which is associated with the signal transduction machinery via heavy chain (HC) proteins that have been generated by productive rearrangement of the immunoglobulin HC genes. The pre-BCR marks a key step of B-cell commitment, as it activates the B-cell-specific signaling cascade and mediates the selection, expansion, and differentiation of cells expressing a productively rearranged HC protein. Another difference between the pre-BCR and conventional BCR might be the initial event that triggers receptor activation, as the pre-BCR is activated in the absence of external ligands, while conventional BCRs require antigen for activation. Nonetheless, the pre-BCR downstream signaling cascade is largely similar to that of the BCR suggesting that the characteristic LC of the pre-BCR mediates important receptor interactions thereby providing distinctive, germ line-encoded features to the pre-BCR. In fact, the SLC enables the pre-BCR to act as a surrogate autoreactive receptor. Here, we outline the structure and function of the pre-BCR and how the autonomous signaling capacity might be a direct consequence of pre-BCR assembly. In addition to its role in early B-cell development, we discuss how the ordered activation of downstream signaling cascades enables the pre-BCR to activate seemingly opposing cellular programs such as proliferation and differentiation.
在发育早期，前体B淋巴细胞表达一种特征性的抗原受体，称为前B细胞受体（pre-BCR）。这种受体与传统的BCR不同，它具有一个种系编码的替代轻链（SLC），该轻链通过重链（HC）蛋白与信号转导机制相关联，而重链蛋白是由免疫球蛋白HC基因的有效重排产生的。前B细胞受体标志着B细胞定向分化的关键步骤，因为它激活B细胞特异性信号级联反应，并介导表达有效重排的HC蛋白的细胞的选择、扩增和分化。前B细胞受体与传统BCR的另一个区别可能是触发受体激活的初始事件，因为前B细胞受体在没有外部配体的情况下被激活，而传统BCR需要抗原才能激活。尽管如此，前B细胞受体下游信号级联反应在很大程度上与BCR相似，这表明前B细胞受体的特征性轻链介导了重要的受体相互作用，从而为前B细胞受体提供了独特的、种系编码的特征。事实上，SLC使前B细胞受体能够作为替代自身反应性受体发挥作用。在这里，我们概述了前B细胞受体的结构和功能，以及自主信号传导能力如何可能是前B细胞受体组装的直接结果。除了其在早期B细胞发育中的作用外，我们还讨论了下游信号级联反应的有序激活如何使前B细胞受体激活看似相反的细胞程序，如增殖和分化。
