Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Nature. 2024 Aug;632(8025):637-646. doi: 10.1038/s41586-024-07729-x. Epub 2024 Jul 31.
Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways are unclear. 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). 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.
鼻腔接种可引发体液免疫应答,从而提供针对空气传播病原体的保护,但上呼吸道中抗原特异性 IgA 分泌细胞的起源和特定免疫生态位尚不清楚。在这里,我们将鼻腺泡结构和鼻甲定义为免疫生态位,它们从鼻相关淋巴组织 (NALT) 募集 IgA 分泌浆细胞。通过完整器官成像,我们证明鼻腔接种可诱导 NALT 黏膜下穹窿中的 B 细胞扩增,随后以 T 细胞依赖的方式侵入定植细菌驱动的慢性生发中心。NALT 生发中心反应的起始需要抗原特异性 T 细胞的预先扩增,这些 T 细胞在滤泡间区域与同源 B 细胞相互作用。NALT 消融和 PSGL-1 阻断(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,主要定位于腺泡结构周围。鼻甲中 CCL28 的表达在接种后增加,并促进 IgA B 细胞归巢到该部位。因此,针对鼻腔接种,腺泡和鼻甲提供了免疫生态位,宿主 NALT 来源的 IgA 分泌细胞。这些细胞事件可以在疫苗设计或上呼吸道过敏反应的治疗中进行干预。