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華中農(nóng)業(yè)大學(xué)團(tuán)隊(duì)解析殼寡糖增強(qiáng)魚類體液免疫的細(xì)胞和分子機(jī)制

2022-01-05 08:06:15   來源:華中農(nóng)業(yè)大學(xué)

  殼寡糖增強(qiáng)草魚體液免疫的細(xì)胞和分子機(jī)制
 
  近日,華中農(nóng)業(yè)大學(xué)水產(chǎn)學(xué)院張永安教授團(tuán)隊(duì)以草魚為研究對(duì)象,解析了殼寡糖誘導(dǎo)魚類B細(xì)胞分化并產(chǎn)生天然IgM,從而增強(qiáng)魚類體液免疫的細(xì)胞和分子機(jī)制。該研究以“Plasmablasts induced by chitosan oligosaccharide secrete natural IgM to enhance the humoral immunity in grass carp”為題在Carbohydrate Polymers上發(fā)表。
 
  殼寡糖(Chitosan Oligosaccharide,COS)是由2-10個(gè)氨基葡萄糖經(jīng)β-1, 4糖苷鍵連接而成的功能性低聚糖,來源于蝦蟹殼,純天然、無毒害、分子量小、水溶性高、易被機(jī)體吸收利用,可作為飼料添加劑顯著提高畜、禽、水產(chǎn)動(dòng)物的免疫力和抗病力并促進(jìn)動(dòng)物生長(zhǎng)。然而,早期的研究多聚焦于殼寡糖對(duì)動(dòng)物先天性免疫細(xì)胞(如巨噬細(xì)胞和樹突狀細(xì)胞)的激活,很少關(guān)注殼寡糖對(duì)適應(yīng)性免疫細(xì)胞(如B細(xì)胞)的活化作用。
 
  為了探究魚類B細(xì)胞活化及抗體產(chǎn)生機(jī)制,張永安團(tuán)隊(duì)首先制備了草魚IgM重鏈的單克隆抗體,發(fā)現(xiàn)健康草魚中存在兩類IgM+ B細(xì)胞亞群,即IgM+ B淋巴細(xì)胞和IgM+ 髓樣細(xì)胞。其中,IgM+ 髓樣細(xì)胞被進(jìn)一步鑒定為類似于哺乳動(dòng)物的漿細(xì)胞,且重組表達(dá)的CD40L和IL-21能夠協(xié)同促進(jìn)IgM+ 漿細(xì)胞的生成和IgM的分泌表明魚類B細(xì)胞能夠被相關(guān)信號(hào)分子顯著誘導(dǎo)分化?;诖?,研究進(jìn)一步發(fā)現(xiàn)殼寡糖能夠與B細(xì)胞表面的甘露糖受體(MR)和整合素(Integrin)結(jié)合而激活下游的信號(hào)通路,最終強(qiáng)烈誘導(dǎo)草魚脾臟IgM+ B淋巴細(xì)胞增殖分化為IgMlo和IgMhi B細(xì)胞亞群,其中IgMlo B細(xì)胞被證實(shí)是一類膜表面低表達(dá)IgM,能夠分泌天然IgM的漿母細(xì)胞。活體實(shí)驗(yàn)進(jìn)一步證實(shí),殼寡糖誘導(dǎo)增殖的IgMlo漿母細(xì)胞可以從脾臟遷移到血液,大量分泌能夠靶向病原相關(guān)分子模式(PAMP)的天然IgM,從而提高魚體的抗病力。研究首次揭示了殼寡糖增強(qiáng)魚類體液免疫的細(xì)胞和分子機(jī)制,為殼寡糖在魚類養(yǎng)殖業(yè)中的應(yīng)用提供了有力的理論支撐。此外,研究還進(jìn)一步明確了魚類B細(xì)胞的先天性免疫屬性,且為研究魚類B細(xì)胞的分化提供了良好的模型。
 
  我校博士生王杰為論文的第一作者,張永安教授和張旭杰副教授為論文的共同通訊作者。該研究得到了國家重點(diǎn)研發(fā)計(jì)劃、國家自然科學(xué)基金以及中央高?;究蒲袠I(yè)務(wù)費(fèi)專項(xiàng)資金的資助。
 
  【英文摘要】
 
  Chitosan oligosaccharide (COS) is an attractive immunopotentiator capable of driving humoral immunity in vertebrates, but its cellular and molecular mechanisms still require elucidation. In this study, COS induced the proliferation and differentiation of splenic IgM+ B cells into IgMlo and IgMhi B cell subsets in grass carp (Ctenopharyngodon idella)。 The IgMlo B cells were further identified as short-lived plasmablasts that secreted natural IgM with binding-abilities to lipopolysaccharide (LPS) and peptidoglycan (PGN)。 Moreover, the mannose receptor (MR) and integrins were discovered and identified as the binding-receptors of COS on IgMlo plasmablasts. The MR synergized with integrins to trigger intracellular signal transduction to boost plasmablast generation and expansion. Notably, IgMlo plasmablasts originally generated in spleen but they migrated into blood to secrete natural IgM, which augmented the serum bactericidal activity. Taken together, this study revealed the cellular and molecular mechanisms of COS-triggered humoral immunity in fish.
 
  論文鏈接:https://www.sciencedirect.com/science/article/pii/S0144861721014600