The Norwegian College of Fishery Science, University of Tromsø, N-9037 Tromsø, Norway.
Dev Comp Immunol. 2010 Jan;34(1):29-41. doi: 10.1016/j.dci.2009.07.009. Epub 2009 Aug 19.
Major histocompatibility complex class II (MHCII) is encoded by polymorphic genes present in vertebrates and expressed predominately in leukocytes. Upon leukocyte differentiation, intracellular MHCII is dynamically redistributed within the cells and it is expressed at maximal levels on mature antigen presenting cells (APCs). In addition, APCs secrete MHCII within endosome-derived vesicles known as exosomes which possess diverse immunomodulatory properties. Genetic and biochemical data have confirmed that piscine leukocytes express the MHCII components as well as costimulatory molecules that are necessary for the function of APCs. However data concerning the biosynthesis and the distribution of the MHCII complex within leukocytes of lower vertebrates is scarce. The presented data demonstrates for the first time that salmon leukocytes secrete vesicles that contain exosomal markers and the abundance of MHCII indicates that these exosomes are released by APCs. The secretion was specifically induced by CpG stimulation in vitro and it was observed only in head kidney leukocytes but not in splenocyte cultures. Flow cytometry revealed that, unlike splenocytes, the majority of the MHCII-positive head kidney leukocytes were Ig-negative and a population of cells expressing high levels of surface MHCII underwent degranulation upon CpG stimulation suggesting that the MHCII-containing exosomes were derived from maturing salmon APCs. Gene expression analyses have further demonstrated that CpG-B, despite its relatively weak proinflammatory activity compared to LPS, induced expression of a larger group of genes involved in regulation of the adaptive immune response.
主要组织相容性复合体 II 类 (MHCII) 由脊椎动物中存在的多态性基因编码，并主要在白细胞中表达。在白细胞分化过程中，细胞内的 MHCII 在细胞内被动态重新分布，并且在成熟的抗原呈递细胞 (APC) 上表达水平最高。此外，APC 会在称为外泌体的内体衍生小泡中分泌 MHCII，外泌体具有多种免疫调节特性。遗传和生化数据证实，鱼类白细胞表达 MHCII 成分以及 APC 功能所必需的共刺激分子。然而，关于低等脊椎动物白细胞中 MHCII 复合物的生物合成和分布的数据很少。所提供的数据首次表明，鲑鱼白细胞分泌含有外泌体标记物的小泡，并且 MHCII 的丰度表明这些外泌体是由 APC 释放的。这种分泌是由 CpG 体外刺激特异性诱导的，仅在头肾白细胞中观察到，而在脾细胞培养物中未观察到。流式细胞术显示，与脾细胞不同，大多数 MHCII 阳性头肾白细胞 Ig 阴性，并且高水平表达表面 MHCII 的细胞群在 CpG 刺激下脱颗粒，表明 MHCII 包含的外泌体来自成熟的鲑鱼 APCs。基因表达分析进一步表明，CpG-B 尽管与 LPS 相比其促炎活性相对较弱，但诱导了更大一组参与适应性免疫反应调节的基因的表达。
