Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; and
J Immunol. 2022 Sep 15;209(6):1095-1107. doi: 10.4049/jimmunol.2200280. Epub 2022 Aug 19.
Mammalian studies have demonstrated that B cell immune responses are regulated by mechanistic target of rapamycin complex 1 (mTORC1) signaling. Teleost fish represent the oldest living bony vertebrates that contain bona fide B cells. So far, whether the regulatory mechanism of mTORC1 signaling in B cells occurred in teleost fish is still unknown. In this study, we developed a fish model by using rapamycin (RAPA) treatment to inhibit mTORC1 signaling and demonstrated the role of mTORC1 signaling in teleost B cells. In support, we found inhibition of mTORC1 signaling by RAPA decreased the phagocytic capacity, proliferation, and Ig production of B cells. Critically, induced specific IgM binding in serum, and these titers were significantly inhibited by RAPA treatment, thus decreasing Ab-mediated agglutination of and significantly increasing the susceptibility of fish upon reinfection. Collectively, our findings elucidated that the mTORC1 pathway is evolutionarily conserved in regulating B cell responses, thus providing a new point for understanding the B cells functions in teleost fish.
哺乳动物研究表明，B 细胞免疫反应受雷帕霉素靶蛋白复合体 1（mTORC1）信号的调节。硬骨鱼类是现存最古老的脊椎动物，它们含有真正的 B 细胞。到目前为止，mTORC1 信号在硬骨鱼类 B 细胞中的调节机制尚不清楚。在这项研究中，我们通过使用雷帕霉素（RAPA）处理来抑制 mTORC1 信号，开发了一种鱼类模型，并证明了 mTORC1 信号在硬骨鱼类 B 细胞中的作用。支持这一观点的是，我们发现 RAPA 抑制 mTORC1 信号会降低 B 细胞的吞噬能力、增殖和 Ig 产生。关键的是，诱导了血清中特异性 IgM 的结合，而 RAPA 处理显著抑制了这些滴度，从而降低了 Ab 介导的对 和 的凝集，并显著增加了鱼类在再次感染时的易感性。总的来说，我们的研究结果阐明了 mTORC1 途径在调节 B 细胞反应方面在进化上是保守的，从而为理解硬骨鱼类 B 细胞的功能提供了一个新的角度。
