Ghosh Sumit, Hoselton Scott A, Schuh Jane M
Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA.
Open Immunol J. 2012 Dec 28;5:46-54. doi: 10.2174/1874226201205010046.
Fungal sensitization in patients with asthma often indicates an unusual disease course in which traditional asthma treatments have little effect and in which morbidity is particularly severe. Airway hyperresponsiveness (AHR), inflammatory infiltrates, smooth muscle hyperplasia, and irreversible fibrotic remodeling of the bronchial architecture are features of allergic fungal asthma. The systemic production of IgE has long been associated with the immunopathogenesis of allergic asthma; however, the role of B lymphocytes and their products in the response to fungal allergens remains unclear. In the present study, we hypothesize that B lymphocytes are recruited to the allergic lung to impact the allergic response. Using a murine fungal aeroallergen model to mimic the human syndrome, we characterized the B cell population in the lung after fungal challenge and found that CD19(+)CD23(+) B2 lymphocyte numbers are increased in the allergic lung in a dynamic process. IgA, IgG(2a), and IgE were prominent in the serum and bronchoalveolar lavage fluid of allergic animals. It was evident that a tissue-centric production of these antibodies was possible. IgA-, IgG-, and IgE-producing cells from the allergic lung were identified by flow cytometry and immunohistochemistry. This study shows for the first time that CD19(+)CD23(+) B2 lymphocyte numbers change in the lung in a dynamic process after inhalation of fungal conidia and their increase has a significant impact on the Ab production in the pulmonary compartment in the context of fungal allergy.
哮喘患者的真菌致敏通常预示着一种不同寻常的病程,在此病程中,传统的哮喘治疗效果甚微,且发病率尤为严重。气道高反应性(AHR)、炎性浸润、平滑肌增生以及支气管结构不可逆的纤维化重塑是变应性真菌性哮喘的特征。长期以来,IgE的全身性产生一直与变应性哮喘的免疫发病机制相关;然而,B淋巴细胞及其产物在对真菌过敏原的反应中的作用仍不清楚。在本研究中,我们假设B淋巴细胞被募集到变应性肺中以影响变应性反应。利用小鼠真菌气传过敏原模型模拟人类综合征,我们对真菌攻击后肺中的B细胞群体进行了表征,发现在一个动态过程中,变应性肺中CD19(+)CD23(+) B2淋巴细胞数量增加。IgA、IgG(2a)和IgE在变应性动物的血清和支气管肺泡灌洗液中含量显著。显然,这些抗体以组织为中心的产生是可能的。通过流式细胞术和免疫组织化学鉴定了来自变应性肺的产生IgA、IgG和IgE的细胞。本研究首次表明,吸入真菌分生孢子后,肺中CD19(+)CD23(+) B2淋巴细胞数量在动态过程中发生变化,并且在真菌过敏的情况下,它们的增加对肺内抗体产生有显著影响。