Blocking of the CXCR4-CXCL12 Interaction Inhibits the Migration of Chicken B Cells Into the Bursa of Fabricius
Blocking of the CXCR4-CXCL12 Interaction Inhibits the Migration of Chicken B Cells Into the Bursa of Fabricius
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DOI：
10.3389/fimmu.2019.03057
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发表时间：
2020-01-10
影响因子：
7.3
通讯作者：
Schusser, Benjamin
中科院分区：
文献类型：
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作者：
Laparidou, Maria;Schlickenrieder, Antonina;Schusser, Benjamin
B细胞首先在鸡中被描述为抗体产生细胞，并以支持其发育的独特器官法氏囊命名。了解介导B细胞早期迁移到腔上囊的不同因素对于B细胞生物学研究至关重要。虽然发现CXCL 12（基质衍生因子1）在哺乳动物中的B淋巴细胞运输中起重要作用，但其在鸡中的作用仍然未知。以往的研究表明，鸡CXCL 12及其受体CXCR 4在法氏囊发育过程中同时表达。在本研究中，我们研究了CXCR 4/CXCL 12相互作用是否介导鸡胚B细胞迁移。我们使用CRISPR/Cas9系统在鸡B细胞中诱导CXCR 4敲除，这导致对CXCL 12的趋化性抑制。这通过过继细胞转移和通过用小抑制剂AMD 3100阻断CXCR 4/CXCL 12相互作用的抑制得到证实。此外，我们发现鸡表现出与小鼠相似的CXCR 4依赖于B细胞受体表达。缺乏B细胞受体的B细胞不能向CXCL 12迁移，并且对CXCL 12刺激没有反应。总之，我们证明了CXCR 4/CXCL 12在鸡体内B细胞发育中的重要性以及B细胞受体在CXCR 4依赖性信号传导中的重要性。
B cells have first been described in chickens as antibody producing cells and were named after the Bursa of Fabricius, a unique organ supporting their development. Understanding different factors mediating the early migration of B cells into the bursa of Fabricius is crucial for the study of B cell biology. While CXCL12 (stromal derived factor 1) was found to play an important role in B lymphocyte trafficking in mammals, its role in the chicken is still unknown. Previous studies indicated that chicken CXCL12 and its receptor CXCR4 are simultaneously expressed during bursal development. In this study, we investigated whether the CXCR4/CXCL12 interaction mediates B cell migration in chicken embryo. We used the CRISPR/Cas9 system to induce a CXCR4 knockout in chicken B cells which led to chemotaxis inhibition toward CXCL12. This was confirmed by adoptive cell transfer and inhibition of the CXCR4/CXCL12 interaction by blocking with the small inhibitor AMD3100. In addition, we found that the chicken exhibits similarities to mice when it comes to CXCR4 being dependent on B cell receptor expression. B cells lacking the B cell receptor failed to migrate toward CXCL12 and showed no response upon CXCL12 stimulation. Overall, we demonstrated the significance of CXCR4/CXCL12 in chicken B cell development in vivo and the importance of the B cell receptor in CXCR4 dependent signaling.