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Immunol."],"abstract":"<jats:p>\n                    This study identifies and characterizes previously unrecognized medullary B cell niches within murine mucosa-draining lymph nodes (LNs), challenging the conventional understanding of LN architecture. Utilizing advanced imaging techniques, including synchrotron radiation-based phase-contrast micro-computed tomography (SR\u00b5CT), correlated high-resolution electron microscopy and immunohistochemistry (IHC), we revealed spherical to ovoid structures termed\n                    <jats:italic>nodules<\/jats:italic>\n                    , being distinct lymphoid compartments consistently localized in the medullary region of mandibular and other mucosa-draining LNs. These nodules were primarily composed of unswitched, non-proliferative CD45R\n                    <jats:sup>+<\/jats:sup>\n                    B cells expressing IgD and IgM, lacking germinal center features or typical activation markers. They were seamlessly integrated into the medullary architecture, surrounded by LYVE-1\n                    <jats:sup>+<\/jats:sup>\n                    lymphatic endothelial cells, and situated in close proximity to medullary high endothelial venules (HEVs), revealed by PNAd staining. Under steady-state conditions, this has not been previously observed in the medullary compartment of LNs but is likely facilitating nodule-like B cell aggregation in mucosa-draining LNs due to sustained low level antigenic stimulation common in mucosal environments and is underpinned by proteomics. Additionally, the nodules displayed a capillary network that closely resembles the vascularization seen in conventional B cell follicles revealed by SR\u00b5CT. Nodule formation occured between two and four weeks postnatally, thus emerging later than B cell follicles, and their abundance showed a tendency to increase with age. Functionally, these nodules appear to represent a quiescent B cell niche, potentially supporting B cell homeostasis, tolerance, or memory-like readiness, and are distinct from pathological hyperplasias. Their preservation in aged LNs, coupled with the absence of lipomatosis, suggests a role in maintaining structural integrity and immune readiness through persistent B cell-stromal interactions. This research challenges the established paradigm of LN microarchitecture and suggests specialized niches for B cell function and lymphocyte trafficking in regions subject to constant antigenic exposure.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1674997","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:36:36Z","timestamp":1763534196000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Follicle-like niches outside the cortex? 3D phase-contrast \u00b5CT revealed medullary B cell nodules in mucosa-draining lymph nodes"],"prefix":"10.3389","volume":"16","author":[{"given":"Paul","family":"Sch\u00fctz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian L.","family":"Schwarzenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennert 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