Jingjing Liu, Liat Stoler-Barak, Hadas Hezroni-Bravyi, Adi Biram, Sacha Lebon, Natalia Davidzohn, Merav Kedmi, Muriel Chemla, David Pilzer, Marina Cohen, Ori Brenner, Moshe Biton, Ziv Shulman
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Initiation of the germinal centre response in the NALT requires pre-expansion of antigen-specific T cells, which interact with cognate B cells in interfollicular regions. NALT ablation and blockade of PSGL-1, which mediates interactions with endothelial cell selectins, demonstrated that NALT-derived IgA-expressing B cells home to the turbinate region through the circulation, where they are positioned primarily around glandular acinar structures. CCL28 expression was increased in the turbinates in response to vaccination and promoted homing of IgA+ B cells to this site. Thus, in response to nasal vaccination, the glandular acini and turbinates provide immunological niches that host NALT-derived IgA-secreting cells. These cellular events could be manipulated in vaccine design or in the treatment of upper airway allergic responses. 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引用次数: 0
摘要
鼻腔疫苗接种会引起体液免疫反应,从而提供对空气传播病原体的保护1,但上呼吸道中抗原特异性 IgA 分泌细胞的来源和特异性免疫龛位还不清楚2。在这里,我们将鼻腺尖状体结构和鼻甲定义为免疫龛位,它们能从鼻腔相关淋巴组织(NALTs)3 中招募分泌 IgA 的浆细胞。NALT 生殖中心反应的启动需要抗原特异性 T 细胞的预先扩增,T 细胞会与叶间区的同源 B 细胞相互作用。NALT消融和阻断PSGL-1(介导与内皮细胞选择素的相互作用)表明,NALT衍生的表达IgA的B细胞通过血液循环进入鼻甲区,它们主要分布在腺尖状结构周围。接种疫苗后,鼻甲中的 CCL28 表达增加,促进了 IgA+ B 细胞向该部位的归巢。因此,在接种鼻腔疫苗后,腺样尖头和鼻甲会提供免疫壁龛,以容纳 NALT 衍生的分泌 IgA 的细胞。这些细胞事件可在疫苗设计或治疗上呼吸道过敏反应时加以控制。
Turbinate-homing IgA-secreting cells originate in the nasal lymphoid tissues
Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens1, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways are unclear2. Here we define nasal glandular acinar structures and the turbinates as immunological niches that recruit IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALTs)3. Using intact organ imaging, we demonstrate that nasal vaccination induces B cell expansion in the subepithelial dome of the NALT, followed by invasion into commensal-bacteria-driven chronic germinal centres in a T cell-dependent manner. Initiation of the germinal centre response in the NALT requires pre-expansion of antigen-specific T cells, which interact with cognate B cells in interfollicular regions. NALT ablation and blockade of PSGL-1, which mediates interactions with endothelial cell selectins, demonstrated that NALT-derived IgA-expressing B cells home to the turbinate region through the circulation, where they are positioned primarily around glandular acinar structures. CCL28 expression was increased in the turbinates in response to vaccination and promoted homing of IgA+ B cells to this site. Thus, in response to nasal vaccination, the glandular acini and turbinates provide immunological niches that host NALT-derived IgA-secreting cells. These cellular events could be manipulated in vaccine design or in the treatment of upper airway allergic responses. Nasal vaccination induces B cell expansion in the nasal-associated lymphoid tissues, followed by homing to the nasal turbinates and glandular acinar structures.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.