Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
Fish Shellfish Immunol. 2019 Feb;85:9-17. doi: 10.1016/j.fsi.2017.10.003. Epub 2017 Oct 5.
In teleost fish, IgM B cells are one of the main responders against inflammatory stimuli in the peritoneal cavity, as IgM B cells dominate the peritoneum after intraperitoneal stimulation, also increasing the levels of secreted IgM. BAFF, a cytokine known to play a major role in B cell biology, has been shown to be up-regulated along with its receptors in the peritoneum of rainbow trout upon antigenic exposure, however, the regulatory mechanisms underneath this response remain unclear. In this study, we have identified two different IgM B cell types residing in the peritoneal cavity of previously vaccinated rainbow trout (Oncorhynchus mykiss): IgDIgMMHCII cells, resembling naïve B cells, and IgDIgMMHCII cells, resembling antibody-secreting cells. Based on their membrane IgM levels, these cell types were named IgM and IgM B cells, respectively. As each of these B cell populations showed a distinct expression pattern for the different BAFF receptors, we studied the effect of BAFF individually on each cell subset. Recombinant BAFF promoted the survival of IgM but not IgM B cells in vitro, resulting in increased levels of IgM-secreting cells. In contrast, BAFF increased the levels of membrane MHC II only on IgM B cells, suggesting different functions on these B cell subsets. Moreover, we also showed that peritoneal IgM B cells expressed BAFF at levels comparable to those seen on myeloid cells. These results point to BAFF as a main regulator of B cell homeostasis in the peritoneal cavity, suggesting that this cytokine can trigger different signals on different peritoneal B cell subsets in a specific manner.
在硬骨鱼类中，IgM B 细胞是对腹腔内炎症刺激的主要反应者之一，因为 IgM B 细胞在腹腔内刺激后占据主导地位，同时增加了分泌 IgM 的水平。BAFF 是一种已知在 B 细胞生物学中起主要作用的细胞因子，已被证明在抗原暴露时会在虹鳟鱼的腹膜中上调其受体及其自身，然而，这种反应背后的调节机制尚不清楚。在这项研究中，我们已经鉴定出两种不同的驻留在先前接种过的虹鳟鱼（Oncorhynchus mykiss）腹腔内的 IgM B 细胞类型：IgD+IgM+MHCII 细胞，类似于幼稚 B 细胞，和 IgD+IgM+MHCII 细胞，类似于分泌抗体的细胞。根据它们的膜 IgM 水平，这两种细胞类型分别命名为 IgM 和 IgM B 细胞。由于这两种 B 细胞群体都表现出不同的 BAFF 受体表达模式，我们研究了 BAFF 对每种细胞亚群的单独作用。重组 BAFF 在体外促进了 IgM 但不促进 IgM B 细胞的存活，导致分泌 IgM 的细胞水平增加。相比之下，BAFF 仅在 IgM B 细胞上增加了膜 MHC II 的水平，表明对这些 B 细胞亚群具有不同的功能。此外，我们还表明，腹膜 IgM B 细胞表达的 BAFF 水平与髓样细胞上观察到的水平相当。这些结果表明 BAFF 是腹膜腔中 B 细胞稳态的主要调节剂，表明该细胞因子可以以特定的方式在不同的腹膜 B 细胞亚群上触发不同的信号。
