Abstract：
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.
摘要：
鼻疫苗接种可引发体液免疫反应，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分泌细胞的起源和特异性免疫功能尚不清楚2。在这里，我们将鼻腺腺泡结构和鼻甲定义为从鼻相关淋巴组织（NALT）3招募分泌IgA的浆细胞的免疫壁n。使用完整的器官成像，我们证明了鼻疫苗在NALT的上皮下圆顶中诱导B细胞扩增，随后以T细胞依赖性方式侵入共生细菌驱动的慢性生发中心。NALT中生发中心反应的启动需要抗原特异性T细胞的预扩增，与卵泡间区域的同源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来源的表达IgA的B细胞通过循环归巢到鼻甲区域，它们主要位于腺腺结构周围。CCL28表达在鼻甲中响应于疫苗接种而增加,并促进IgA+B细胞到该位点的归巢。因此，作为对鼻腔疫苗接种的反应，腺泡和鼻甲提供了宿主NALT衍生的IgA分泌细胞的免疫生态位。这些细胞事件可以在疫苗设计或上气道变态反应的治疗中操纵。
