{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:22Z","timestamp":1790744542861,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support a model in which lymph node microanatomy imprints a distinct mGC state, diversifying humoral immune architecture during respiratory viral infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1930085","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:52:10Z","timestamp":1790743930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial compartmentalization shapes distinct germinal center states during respiratory viral 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