Animal Health Research Center, National Institute for Agricultural and Food Research and Technology, Valdeolmos 28130, Madrid, Spain.
Animal Health Research Center, National Institute for Agricultural and Food Research and Technology, Valdeolmos 28130, Madrid, Spain
J Immunol. 2021 Apr 15;206(8):1765-1775. doi: 10.4049/jimmunol.2000762. Epub 2021 Mar 24.
TNF superfamily (TNFSF) members, such as BAFF and a proliferation-inducing ligand (APRIL), emerged in vertebrates as key regulators of B cell homeostasis and activation. Many cartilaginous and teleost fish contain an additional gene, designated as BAFF- and APRIL-like molecule (BALM), of unknown function and lost in tetrapods. In this study, we have performed a wide characterization of the functions of BALM on naive B cells for the first time, to our knowledge, in teleosts using rainbow trout () as a model. Similar to BAFF and APRIL, BALM increased the survival and promoted the proliferation of peripheral blood IgM B cells and cooperated with BCR cross-linking to increase the proliferation rate of IgM B cells. BALM also seemed to be a differentiating factor for trout IgM B cells, as it increased IgM secretion and increased cell size. Additionally, BALM appeared to increase the Ag-presenting properties of IgM B cells, augmenting MHC class II surface expression and upregulating the phagocytic capacity of these cells. Finally, the fact that there was no synergy between BALM and BAFF/APRIL in any of these functions strongly suggests that BALM signals through the same receptors as BAFF and APRIL to carry out its functions. This hypothesis was further supported in competitive BALM binding assays. The results presented provide relevant information for understanding how these TNFSF members cooperate in teleost fish to regulate B cell functionality, helping us to interpret the evolutionary relations between molecules of this family.
肿瘤坏死因子超家族（TNFSF）成员，如 BAFF 和增殖诱导配体（APRIL），在脊椎动物中作为 B 细胞动态平衡和激活的关键调节剂出现。许多软骨鱼和硬骨鱼含有一个额外的基因，称为 BAFF 和 APRIL 样分子（BALM），其功能未知，在四足动物中丢失。在这项研究中，我们首次在硬骨鱼中对 BALM 对幼稚 B 细胞的功能进行了广泛的表征，据我们所知，使用虹鳟鱼（）作为模型。与 BAFF 和 APRIL 相似，BALM 增加了外周血 IgM B 细胞的存活率并促进了其增殖，并与 BCR 交联协同作用增加了 IgM B 细胞的增殖速度。BALM 似乎也是鳜 IgM B 细胞的分化因子，因为它增加了 IgM 的分泌并增加了细胞大小。此外，BALM 似乎增加了 IgM B 细胞的抗原呈递特性，上调了这些细胞的 MHC Ⅱ类表面表达并上调了其吞噬能力。最后，BALM 与 BAFF/APRIL 之间在任何这些功能中都没有协同作用，这强烈表明 BALM 通过与 BAFF 和 APRIL 相同的受体发出信号以发挥其功能。这一假设在竞争性 BALM 结合测定中得到了进一步支持。所呈现的结果提供了有关理解这些 TNFSF 成员如何在硬骨鱼中合作调节 B 细胞功能的相关信息，有助于我们解释该家族分子之间的进化关系。
