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用2/6病毒样颗粒经鼻内免疫诱导的小鼠轮状病毒特异性B细胞的分布及表型

Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles.

作者信息

Ogier Agathe, Franco Manuel A, Charpilienne Annie, Cohen Jean, Pothier Pierre, Kohli Evelyne

机构信息

Microbiologie Médicale et Moléculaire, EA562, UFRs Médecine et Pharmacie, Laboratoire de Virologie CHU, Dijon, France.

出版信息

Eur J Immunol. 2005 Jul;35(7):2122-30. doi: 10.1002/eji.200526059.

DOI:10.1002/eji.200526059
PMID:15948217
Abstract

Virus-like particles containing the rotavirus (RV) internal proteins VP2 and VP6 (2/6-VLP) have been shown to induce serum and fecal antibodies as well as protection in mice after intranasal administration with a mutant of E. coli toxin, LT-R192G. To better understand the origin of fecal IgA induced by this protocol, we studied the RV-specific B cell response in systemic and mucosal lymphoid tissues using a flow cytometry assay that allows quantification and phenotypic characterization of RV-specific B lymphocytes. We also assessed the RV-specific antibody-secreting cells in the spleen and intestinal lamina propria (ILP). A remarkably high frequency of RV-specific B cells was found in the respiratory lymphoid tissues and spleen, of which only a minority expressed the alpha4beta7 integrin (intestinal homing receptor). In contrast, but in accordance with alpha4beta7 expression at the induction site, a very low response was observed in intestinal lymphoid tissues (mesenteric lymph nodes and ILP), which did not increase after a second immunization. Thus, intranasal immunization with a nonreplicating antigen does not induce an important number of RV-specific B cells with an intestinal homing profile.

摘要

含有轮状病毒(RV)内部蛋白VP2和VP6的病毒样颗粒(2/6-VLP)已被证明,在用大肠杆菌毒素突变体LT-R192G经鼻给药后,可在小鼠体内诱导血清和粪便抗体以及产生保护作用。为了更好地理解该方案诱导的粪便IgA的来源,我们使用流式细胞术检测方法研究了全身和黏膜淋巴组织中RV特异性B细胞反应,该方法可对RV特异性B淋巴细胞进行定量和表型特征分析。我们还评估了脾脏和肠固有层(ILP)中RV特异性抗体分泌细胞。在呼吸道淋巴组织和脾脏中发现了频率极高的RV特异性B细胞,其中只有少数细胞表达α4β7整合素(肠道归巢受体)。相比之下,与诱导部位的α4β7表达情况一致,在肠道淋巴组织(肠系膜淋巴结和ILP)中观察到的反应非常低,二次免疫后也没有增加。因此,用非复制性抗原进行鼻内免疫不会诱导大量具有肠道归巢特征的RV特异性B细胞。

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Intrarectal immunization with rotavirus 2/6 virus-like particles induces an antirotavirus immune response localized in the intestinal mucosa and protects against rotavirus infection in mice.用轮状病毒2/6病毒样颗粒进行直肠内免疫可诱导肠道黏膜局部的抗轮状病毒免疫反应,并保护小鼠免受轮状病毒感染。
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Rectal immunization with rotavirus virus-like particles induces systemic and mucosal humoral immune responses and protects mice against rotavirus infection.用轮状病毒样颗粒进行直肠免疫可诱导全身和黏膜体液免疫反应,并保护小鼠免受轮状病毒感染。
J Virol. 2006 Feb;80(4):1752-61. doi: 10.1128/JVI.80.4.1752-1761.2006.