小柯机器人

美国芝加哥大学Marcus R. Clark和Malay Mandal课题组合作揭示了CXCR4信号指导Igk基因重组和晚期B淋巴细胞形成的分子机制。这一研究成果2019年9月2日在线发表于《自然—免疫学》。

他们证明前B细胞抗原受体（pre-BCR）启动由转录因子干扰素调节因子4和趋化因子受体C-X-C基序（CXCR4）介导的前馈扩增环。通过CXC基序趋化因子配体12连接CXCR4，并激活促分裂原活化的蛋白激酶细胞外信号调节激酶，然后指导小的前B细胞和未成熟B细胞的发育，包括协调细胞周期的完成，pre-BCR 的抑制，Igk重组和BCR表达。相比之下，pre-BCR表达和逃避白细胞介素-7对B细胞发育转录和表观遗传进程仅有轻微的影响。这些数据显示CXCR4在协调晚期B淋巴细胞形成中的直接和核心作用。此外，在先前发现的背景下，他们的数据提供了三受体系统，这足以概括体外B淋巴细胞形成的基本特征。

据了解，在B淋巴细胞形成过程中，pre-BCR的激活与细胞周期完成和Igk基因重组有关。然而，pre-BCR如何调解这些功能仍不清楚。

附：英文原文

Title: CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

Author: Malay Mandal, Michael K. Okoreeh, Domenick E. Kennedy, Mark Maienschein-Cline, Junting Ai, Kaitlin C. McLean, Natalya Kaverina, Margaret Veselits, Iannis Aifantis, Fotini Gounari, Marcus R. Clark

Issue&Volume: 2019-09-02

Abstract: In B lymphopoiesis, activation of the pre-B cell antigen receptor (pre-BCR) is associated with both cell cycle exit and Igk recombination. Yet how the pre-BCR mediates these functions remains unclear. Here, we demonstrate that the pre-BCR initiates a feed-forward amplification loop mediated by the transcription factor interferon regulatory factor 4 and the chemokine receptor C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 ligation by C-X-C motif chemokine ligand 12 activates the mitogen-activated protein kinase extracellular-signal-regulated kinase, which then directs the development of small pre- and immature B cells, including orchestrating cell cycle exit, pre-BCR repression, Igk recombination and BCR expression. In contrast, pre-BCR expression and escape from interleukin-7 have only modest effects on B cell developmental transcriptional and epigenetic programs. These data show a direct and central role for CXCR4 in orchestrating late B cell lymphopoiesis. Furthermore, in the context of previous findings, our data provide a three-receptor system sufficient to recapitulate the essential features of B lymphopoiesis in vitro.

DOI: 10.1038/s41590-019-0468-0

Source:https://www.nature.com/articles/s41590-019-0468-0

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex