Editors' ChoiceImmunology

Antibodies go with the lymphatic flow

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Science Translational Medicine  06 Nov 2019:
Vol. 11, Issue 517, eaaz7147
DOI: 10.1126/scitranslmed.aaz7147

Abstract

Lymph flow through Peyer’s patches enhances mucosal antibody production.

After infection, lymph fluid flows from peripheral tissues to the draining lymph node, carrying along tissue antigens including bacteria and viruses. Lymph reaching the node passes through a series of sinuses, where antigen presenting cells can access lymph-borne particulates and display them to naïve lymphocytes. Lymph first encounters a subcapsular sinus lined with macrophages that relay captured antigen to underlying B cell follicles. In between follicles, a series of small channels formed by stromal cells connect the subcapsular sinus to the node’s interior paracortex, also referred to as the T cell zone. Small molecules carried in lymph can enter these channels, called conduits, and are conveyed through the T cell zone to the high endothelial venules that are the sites of lymphocyte entry from the blood. Until now, the importance of the conduits during immune responses has been unclear because experimentally perturbing lymph flow specifically through nodal conduits has proven difficult.

To examine the impact of conduits on adaptive immunity, Chang et al. investigated Peyer’s patches, organized lymphoid structures in the intestine. Like lymph nodes, Peyer’s patches have B cell follicles and T cell zones; however, they lack several key features of lymph nodes, including subcapsular sinuses. Therefore, Chang et al. first demonstrated that, like lymph nodes, Peyer’s patches contain a conduit system formed by stromal cells that transports small, ingested proteins directly from the intestines. Similar to lymph nodes, Peyer’s patch conduits connect directly to the blood vessels through which lymphocytes enter. The authors then used two clever approaches to manipulate lymph flow through Peyer’s patch conduits: increasing the osmolarity in the intestines and ablating the mechanosensory molecule Piezo1 in Peyer’s patch stromal cells. Both approaches dramatically altered the structure of conduit-connected blood vessels, which could no longer fully recruit lymphocytes. This reduction in lymphocyte entry impacted mucosal antibody responses to vaccination. Although this study sheds important light on conduit function, the altered Peyer’s cellularity makes it difficult to assess the importance of conduit-antigen delivery during adaptive immune responses. Regardless, these findings reveal that there are still unappreciated factors, including solutes in the intestine, poised to shape mucosal antibody responses.

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