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@ARTICLE{Schuetz:641740,
      author       = {Schuetz, Paul and Schwarzenberg, Florian Lennart and Weber,
                      Lennert and Hammel, Joerg and Siebels, Bente and Nissen,
                      Paula and Leising, Nenya and Jarick, Katja J. and
                      Walkenfort, Bernd and Irvine, Sarah and Bartl, Jasmin and
                      Herzen, Julia and Lohr, Christian and Wuelfing, Clemens and
                      Henne, Stephan},
      title        = {{F}ollicle-like niches outside the cortex? 3{D}
                      phase-contrast µ{CT} revealed medullary {B} cell nodules in
                      mucosa-draining lymph nodes},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {PUBDB-2025-05151},
      pages        = {1674997},
      year         = {2025},
      abstract     = {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
                      (SRµCT), correlated high-resolution electron microscopy and
                      immunohistochemistry (IHC), we revealed spherical to ovoid
                      structures termed nodules, 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+ 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+ 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 SRµCT. 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.},
      cin          = {FS DOOR-User / Hereon / TUM},
      ddc          = {610},
      cid          = {$I:(DE-H253)FS_DOOR-User-20241023$ /
                      I:(DE-H253)Hereon-20210428 / I:(DE-588b)36241-4},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3) / FS-Proposal: I-20220257
                      (I-20220257) / FS-Proposal: BAG-20240009 (BAG-20240009) /
                      DFG project G:(GEPRIS)274299086 -
                      Feldemissions-Rasterelektronenmikroskop (274299086) / SFB
                      1328 A07 - Astrozytäre und neuronale cAMP-Signalgebung bei
                      Neuroinflammation (A07) (404539526) / DFG project
                      G:(GEPRIS)518551069 - Massenspektrometrie-System mit
                      Einzel-Zell-Sensitivität für quantitative Proteomik
                      (518551069)},
      pid          = {G:(DE-HGF)POF4-6G3 / G:(DE-H253)I-20220257 /
                      G:(DE-H253)BAG-20240009 / G:(GEPRIS)274299086 /
                      G:(GEPRIS)404539526 / G:(GEPRIS)518551069},
      experiment   = {EXP:(DE-H253)P-P05-20150101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.3389/fimmu.2025.1674997},
      url          = {https://bib-pubdb1.desy.de/record/641740},
}