Aix-Marseille Université, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Division of Immunology, Transplantation and Infectious Diseases and Experimental Imaging Center, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
J Exp Med. 2018 Dec 3;215(12):2972-2983. doi: 10.1084/jem.20180344. Epub 2018 Nov 14.
Immunoglobulin M (IgM) is the first type of antibody produced during acute infections and thus provides an early line of specific defense against pathogens. Being produced in secondary lymphoid organs, IgM must rapidly be exported to the blood circulation. However, it is currently unknown how such large pentameric molecules are released from lymph nodes (LNs). Here, we show that upon immunization, IgM transiently gains access to the luminal side of the conduit system, a reticular infrastructure enabling fast delivery of tissue-derived soluble substances to the LN parenchyma. Using microinjections of purified IgM, we demonstrate that conduit-associated IgM is delivered by neither the afferent lymph nor the blood, but is locally conveyed by conduits. Exploiting in vivo models, we further demonstrate that conduit-associated IgM is locally and transiently produced by activated, antigen-specific B cells migrating in the T cell zone. Thus, our study reveals that the conduit system is coopted by B cells to rapidly export secreted IgM out of LNs.
免疫球蛋白 M(IgM)是急性感染期间产生的第一种抗体,因此为病原体提供了早期的特异性防御线。IgM 在次级淋巴器官中产生,必须迅速输出到血液循环中。然而,目前尚不清楚如此大的五聚体分子如何从淋巴结(LN)中释放出来。在这里,我们表明,在免疫接种后,IgM 暂时获得了对管道系统腔侧的访问权限,该管道系统是一种网状基础设施,可将组织衍生的可溶性物质快速输送到 LN 实质中。使用纯化的 IgM 的微注射,我们证明管道相关的 IgM 既不是通过输入淋巴管也不是通过血液来输送的,而是由管道局部输送的。利用体内模型,我们进一步证明,在 T 细胞区迁移的激活的、抗原特异性 B 细胞局部和短暂地产生与管道相关的 IgM。因此,我们的研究表明,管道系统被 B 细胞利用来快速将分泌的 IgM 从 LN 中输出。