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Peer-reviewedCC BYFrontiers in immunology

Spatial compartmentalization shapes distinct germinal center states during respiratory viral infection

  • Dong-Yeon Kim1
  • YoungMin Woo1
  • Taehwan Oh1
  • Green Kim1
  • Seung Ho Baek1
  • Eun-Ha Hwang1
  • Gukhui Min1
  • Miji Kim1
  • You Jung An1
  • Yujin Kim1
  • Kyong-Cheol Ko2
  • Jung Joo Hong1
  1. 1National Primate Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , , ,
  2. 2Korea Preclinical Evaluation Center, KRIBB , ,
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Abstract

Background: Germinal centers (GCs) typically arise within the lymph node cortex, where follicular dendritic cell (FDC) networks and follicular helper T cells coordinate B-cell expansion, affinity maturation, and durable immunity. Whether proliferating B-cell aggregates in the medulla engage bona fide GC programs or instead represent a distinct GC-like differentiation state remains unresolved.

Methods: In this study, using mediastinal lymph nodes from SARS-CoV-2-infected cynomolgus macaques, we combined immunofluorescence with Xenium spatial transcriptomics to identify LYVE1+ sinus-associated medullary GC structures (mGCs) alongside conventional cortical GCs (cGCs).

Results: mGCs shared core GC-associated modules with cGCs but showed niche-divergent features, including increased expression of PRDM1, MZB1, and VWF and decreased expression of IRF8, CD27, and CD86. mGCs retained organized follicular architecture but showed lower CD4+ T and GC B cell densities, greater plasma cell representation, and enrichment of pDCs, NK cells, and stromal populations. Compared with cGCs, mGCs lacked polarized CD35+ FDC and CD3+ T cell network topology, exhibited reduced CXCL12 availability, and showed a higher IgM/IgG ratio. During early reinfection, medullary secondary follicles contracted sharply and were associated with higher Foxp3+ cell density.

Conclusion: These findings support a model in which lymph node microanatomy imprints a distinct mGC state, diversifying humoral immune architecture during respiratory viral infection.

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Cite

BibTeXRIS
BibTeX
@article{kim2026spatial,
  title = {{Spatial compartmentalization shapes distinct germinal center states during respiratory viral infection}},
  author = {Dong-Yeon Kim and YoungMin Woo and Taehwan Oh and Green Kim and Seung Ho Baek and Eun-Ha Hwang and Gukhui Min and Miji Kim and You Jung An and Yujin Kim and Kyong-Cheol Ko and Jung Joo Hong},
  journal = {Frontiers in immunology},
  year = {2026},
  month = sep,
  doi = {10.3389/fimmu.2026.1930085},
  url = {https://europepmc.org/article/PMC/PMC13661466},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Spatial compartmentalization shapes distinct germinal center states during respiratory viral infection
AU  - Dong-Yeon Kim
AU  - YoungMin Woo
AU  - Taehwan Oh
AU  - Green Kim
AU  - Seung Ho Baek
AU  - Eun-Ha Hwang
AU  - Gukhui Min
AU  - Miji Kim
AU  - You Jung An
AU  - Yujin Kim
AU  - Kyong-Cheol Ko
AU  - Jung Joo Hong
PY  - 2026
DA  - 2026/09/30
JO  - Frontiers in immunology
DO  - 10.3389/fimmu.2026.1930085
UR  - https://europepmc.org/article/PMC/PMC13661466
AB  - Background: Germinal centers (GCs) typically arise within the lymph node cortex, where follicular dendritic cell (FDC) networks and follicular helper T cells coordinate B-cell expansion, affinity maturation, and durable immunity. Whether proliferating B-cell aggregates in the medulla engage bona fide GC programs or instead represent a distinct GC-like differentiation state remains unresolved.  Methods: In this study, using mediastinal lymph nodes from SARS-CoV-2-infected cynomolgus macaques, we combined immunofluorescence with Xenium spatial transcriptomics to identify LYVE1+ sinus-associated medullary GC structures (mGCs) alongside conventional cortical GCs (cGCs).  Results: mGCs shared core GC-associated modules with cGCs but showed niche-divergent features, including increased expression of PRDM1, MZB1, and VWF and decreased expression of IRF8, CD27, and CD86. mGCs retained organized follicular architecture but showed lower CD4+ T and GC B cell densities, greater plasma cell representation, and enrichment of pDCs, NK cells, and stromal populations. Compared with cGCs, mGCs lacked polarized CD35+ FDC and CD3+ T cell network topology, exhibited reduced CXCL12 availability, and showed a higher IgM/IgG ratio. During early reinfection, medullary secondary follicles contracted sharply and were associated with higher Foxp3+ cell density.  Conclusion: These findings support a model in which lymph node microanatomy imprints a distinct mGC state, diversifying humoral immune architecture during respiratory viral infection.
SN  - 1664-3224
ER  -