Journal Article

PUBDB-2025-05151

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Follicle-like niches outside the cortex? 3D phase-contrast µCT revealed medullary B cell nodules in mucosa-draining lymph nodes

Schuetz, P.Extern* ; Schwarzenberg, F. L. (Corresponding author)Extern*DESY* ; Weber, L.Extern* ; Hammel, J.HZG*Hereon* ; Siebels, B. ; Nissen, P. ; Leising, N. ; Jarick, K. J. ; Walkenfort, B.Extern* ; Irvine, S.Extern*Hereon* ; Bartl, J.Extern* ; Herzen, J.Extern* ; Lohr, C. ; Wuelfing, C. (Last author)Extern* ; Henne, S. (Last author)Extern*

2025
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fimmu.2025.1674997  doi:10.3204/PUBDB-2025-05151

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.

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Contributing Institute(s):

1. FS DOOR-User (FS DOOR-User)
2. Helmholtz-Zentrum Hereon (Hereon)
3. Technische Universität München (TUM)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. FS-Proposal: I-20220257 (I-20220257) (I-20220257)
3. FS-Proposal: BAG-20240009 (BAG-20240009) (BAG-20240009)
4. DFG project G:(GEPRIS)274299086 - Feldemissions-Rasterelektronenmikroskop (274299086) (274299086)
5. SFB 1328 A07 - Astrozytäre und neuronale cAMP-Signalgebung bei Neuroinflammation (A07) (404539526) (404539526)
6. DFG project G:(GEPRIS)518551069 - Massenspektrometrie-System mit Einzel-Zell-Sensitivität für quantitative Proteomik (518551069) (518551069)

Experiment(s):

1. PETRA Beamline P05 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
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