Spatial compartmentalization shapes distinct germinal center states during respiratory viral infection.

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.