Germinal center formation and local immunoglobulin E (IgE) production in the lung after an airway antigenic challenge
Germinal center formation and local immunoglobulin E (IgE) production in the lung after an airway antigenic challenge
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DOI：
10.1084/jem.184.6.2353
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发表时间：
1996-12-01
影响因子：
15.3
通讯作者：
Bonnefoy, JY
中科院分区：
文献类型：
--
作者：
Chvatchko, Y;KoscoVilbois, MH;Bonnefoy, JY
呼吸道炎症在哮喘的发病机制中起着核心作用。然而，在过敏性炎症过程中，所有类型的细胞在气道高反应性和组织病理学的发展和维持中的确切作用尚不清楚。小鼠外周致敏后，经多个气管(I.T.)激发。注射卵清蛋白(OVA)会导致嗜酸性粒细胞增多、单核细胞浸润和呼吸道上皮细胞改变，类似于哮喘(Blyth，D.I.，M.S.Pedrick，T.J.Savage，E.M.Hessel和D.Fattah)。1996年。上午好。J·雷皮尔(J.Respir)。细胞摩尔比奥尔。14：425-438)。为了进一步研究细胞浸润的性质，对OVA和生理盐水处理的小鼠的肺进行了组织学和免疫组织化学处理。观察到的最显著的特征之一是在发炎的肺实质内形成生发中心。此外，在其质膜上出现了带有OVA的滤泡树突状细胞(FDCs)，并且在这些部位附近出现了OVA特异性的产生IgG1、IgE和IgA的浆细胞。从肺中分离细胞后，在体外对浆细胞数量和抗体产生进行定量，以证实实质内产生了抗原特异性免疫球蛋白(Ig)。这些分析证实，原位观察到的同工型是一种分泌型产物。由于IgE依赖机制被认为是哮喘发病机制的核心，因此评估了气道高反应性。接受肺部炎症的小鼠有高反应，而对照组保持在基线水平。这些数据表明，通过诱导FDC网络和生发中心，抗原驱动的B细胞分化发生在炎症肺的实质中。然后，这些生发中心将提供局部来源的分泌IgE的浆细胞，这些细胞有助于释放介导肺部炎症过程的因子。
Airway inflammation plays a central role in the pathogenesis of asthma. However, the precise contribution of all cell types in the development and maintenance of airway hyperreactivity and histopathology during allergic inflammation remains unclear. After sensitization of mice in the periphery, challenge by multiple intratracheal (i.t.) instillations of ovalbumin (OVA) results in eosinophilia, mononuclear cell infiltration, and airway epithelial changes analogous to that seen in asthma (Blyth, D.I., M.S. Pedrick, T.J. Savage, E.M. Hessel, and D. Fattah. 1996. Am. J. Respir. Cell Mol. Biol. 14:425-438). To investigate further the nature of the cellular infiltrate, lungs from OVA-versus saline-treated mice were processed for histology and immunohistochemistry. One of the most striking features observed was the formation of germinal centers within the parenchyma of the inflamed lungs. In addition, follicular dendritic cells (FDCs) bearing OVA on their plasma membranes appeared and, adjacent to these sites, OVA-specific IgG1-, IgE-, and IgA-producing plasma cells emerged. To confirm that antigen-specific immunoglobulins (Ig) were being produced within the parenchyma, plasma cell number and antibody production were quantitated in vitro after isolation of cells from the lung. These assays confirmed that the isotypes observed in situ were a secreted product. As IgE-dependent mechanisms have been implicated as being central to the pathogenesis of bronchial asthma, airway hyperresponsiveness was evaluated. The mice undergoing lung inflammation were hyperresponsive, while the control group remained at baseline. These data demonstrate that antigen-driven differentiation of B cells via induction of an FDC network and germinal centers occurs in the parenchyma of inflamed lungs. These germinal centers would then provide a local source of IgE-secreting plasma cells that contribute to the release of factors mediating inflammatory processes in the lung.