Animal Health Research Center (CISA-INIA), Valdeolmos, 28130, Madrid, Spain.
Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, United Kingdom.
Dev Comp Immunol. 2020 Oct;111:103752. doi: 10.1016/j.dci.2020.103752. Epub 2020 May 22.
In mammals, conventional B (B2) cells are activated within lymphoid follicles through a close relationship with T follicular helper (Tfh) cells. The interaction between CD40 expressed on B cells and its ligand (CD40L) expressed on Tfh cells is a key signal that regulates the formation of germinal centers (GCs), B cell survival, proliferation and differentiation to plasma cells (PCs) or memory cells. Additionally, certain soluble cytokines produced by T cells also strongly condition the outcome of this interaction. Despite the many differences found between fish B cells and mammalian B2 cells, and the lack of conventional GCs, rainbow trout IgM B cells have been shown to be stimulated by CD40L, however, whether cytokines commonly produced by T cells can further modulate this response has never been addressed to date. Thus, in this study, we determined the effects of recombinant rainbow trout adaptive cytokines interleukin 2B (IL-2B), IL-4/13A, IL-4/13B, IL-10 and IL-21 (cytokines known to activate B cells in mammals) on splenic IgM B cells alone or in combination with CD40L. We studied how these cytokines and CD40L cooperated to promote IgM B cell survival, proliferation and IgM secretion. The results obtained provide valuable information for the first time in teleost fish on how different T cell signals cooperate to activate B cells in the absence of GCs.
在哺乳动物中，传统的 B（B2）细胞通过与滤泡辅助性 T（Tfh）细胞的密切关系在淋巴滤泡中被激活。B 细胞上表达的 CD40 与其在 Tfh 细胞上表达的配体（CD40L）之间的相互作用是调节生发中心（GC）形成、B 细胞存活、增殖和分化为浆细胞（PC）或记忆细胞的关键信号。此外，T 细胞产生的某些可溶性细胞因子也强烈影响这种相互作用的结果。尽管鱼类 B 细胞和哺乳动物 B2 细胞之间存在许多差异，而且缺乏传统的 GC，但已表明虹鳟 IgM B 细胞可被 CD40L 刺激，然而，T 细胞通常产生的细胞因子是否可以进一步调节这种反应，迄今为止尚未得到解决。因此，在这项研究中，我们确定了重组虹鳟适应性细胞因子白细胞介素 2B（IL-2B）、IL-4/13A、IL-4/13B、IL-10 和 IL-21（已知在哺乳动物中激活 B 细胞的细胞因子）对单独或与 CD40L 一起对脾脏 IgM B 细胞的影响。我们研究了这些细胞因子和 CD40L 如何合作促进 IgM B 细胞存活、增殖和 IgM 分泌。获得的结果首次为硬骨鱼类提供了有价值的信息，说明了在没有 GC 的情况下，不同的 T 细胞信号如何合作激活 B 细胞。
