Profiling Atlantic salmon B cell populations: CpG-mediated TLR-ligation enhances IgM secretion and modulates immune gene expression.
Profiling Atlantic salmon B cell populations: CpG-mediated TLR-ligation enhances IgM secretion and modulates immune gene expression.
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DOI：
10.1038/s41598-018-21895-9
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发表时间：
2018-02-23
影响因子：
4.6
通讯作者：
Jørgensen JB
中科院分区：
文献类型：
--
作者：
Jenberie S;Thim HL;Sunyer JO;Skjødt K;Jensen I;Jørgensen JB
虽然TLR激活的通路是哺乳动物B细胞反应的关键调节因子，但它们对硬骨B细胞的影响几乎没有得到解决。在这里，大西洋鲑鱼B细胞对TLR配体的反应潜力是通过展示在磁性分离的IgM+细胞中核酸感应TLRs的结构性表达而显示的。在识别硬骨鱼CpG的两种受体中，TLR9是最主要的受体，其表达水平是Tlr21的10倍以上。在CpG刺激下，头肾(HK)和脾IgM+细胞的IgM分泌增加，而血B细胞受到轻微影响。结果提示，CpG直接影响鲑鱼B细胞分化为抗体分泌细胞。在未经处理的对照组中也检测到IGM分泌，同样在香港来源的人群中检测到最高水平，这意味着在该组织中存在持续性ASCs。在所有组织中，IgM+细胞表达高水平的MHCII，提示具有抗原提呈功能。CpG处理后，共刺激分子CD83和CD40上调，而CD86在相同条件下下调。最后，IFNA1在CpG刺激下在所有组织中上调，而ifnb则明显上调，这表明鲑鱼IgM+B细胞表现出I型干扰素反应。
While TLR-activated pathways are key regulators of B cell responses in mammals, their impact on teleost B cells are scarcely addressed. Here, the potential of Atlantic salmon B cells to respond to TLR ligands was shown by demonstrating a constitutive expression of nucleic-acid sensing TLRs in magnetic sorted IgM+ cells. Of the two receptors recognizing CpG in teleosts, tlr9 was the dominating receptor with over ten-fold higher expression than tlr21. Upon CpG-stimulation, IgM secretion increased for head kidney (HK) and splenic IgM+ cells, while blood B cells were marginally affected. The results suggest that CpG directly affects salmon B cells to differentiate into antibody secreting cells (ASCs). IgM secretion was also detected in the non-treated controls, again with the highest levels in the HK derived population, signifying that persisting ASCs are present in this tissue. In all tissues, the IgM+ cells expressed high MHCII levels, suggesting antigen-presenting functions. Upon CpG-treatment the co-stimulatory molecules cd83 and cd40 were upregulated, while cd86 was down-regulated under the same conditions. Finally, ifna1 was upregulated upon CpG-stimulation in all tissues, while a restricted upregulation was evident for ifnb, proposing that salmon IgM+ B cells exhibit a type I IFN-response.
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