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Characterization of cellular and extracellular regulators of lymphoid organogenesis in the developing bursa of Fabricius

english

Szőcs Emőke

Molecular Medicine Division

Dr. Várnai Péter

Szülészeti és Nőgyógyászati Klinika, Üllői úti részleg, előadóterem

2026-12-01 14:00:00

Embryology, Theoretical, Experimental and Clinical Developmental Biology

Dr. Nagy Nándor

Dr. Nagy Nándor

Dr. Jakus Zoltán Péter

Dr. Balogh Péter

Dr. Buzás Edit

Dr. Cervenák László

Dr. Homolya László

The bursa of Fabricius (BF) is a unique primary lymphoid organ essential for B cell development in birds, that provides a highly specialized and selective microenvironment for the proliferation and differentiation of early precursors. While the function of the medulla in bursal lymphoid follicles is well characterized, the steps of BF organogenesis from the initial induction of epithelial follicle buds to the emergence and regulatory function of the cortical compartment are still not fully understood. Here, we characterize two critical, temporally distinct phases of BF development: the inductive mechanisms that drive lymphoid follicle bud formation and post-hatch extracellular matrix-chemokine interactions that govern B cell migration and egress to the periphery. Using wild-type and CSF1R-eGFP transgenic chick embryos, combined with chick-duck chimeras and chick-quail tissue recombination, we identify a novel EIV-E12+ lymphoid follicle inducer cell population. Experimental depletion models demonstrate that these cells are distinct from B cell and dendritic cell precursors and are capable of inducing follicle bud formation. Following early follicle formation, the BF undergoes further structural maturation with the development of the follicular cortex. Using immunochemistry and RNAscope in situ hybridization, we show that the cortex of lymphoid follicles is supported by desmin+/vimentin+ mesenchymal reticular cells that secrete CXCL12 and tenascin-C in the cortical microenvironment. Embryo manipulation experiments using a Shh-RCAS retrovirus reveal that tenascin-C acts as a potent regulator of B cell migration and experimental overexpression actively disrupts B cell homing and follicle formation. In the adult BF, tenascin-C interacts with the CXCL12 chemokine to regulate B cell egress. We show that CXCR4high B cells must downregulate the CXCR4 receptor to successfully navigate through the CXCL12 and tenascin-C-rich cortical network, before they can exit the bursa to reach the periphery. Together, these data present a comprehensive model of BF ontogenesis and provide vital new insights into the dynamic, stage-specific microenvironmental cues that control primary lymphoid organ development.