Viktória Halasy, Nóra Fejszák, Tamás Kovács, Lili Orbán, Nándor Nagy
Laboratory of Stem Cells and Experimental Embryology, Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Introduction: The bursa of Fabricius (BF) is a central lymphoid organ of the birds responsible for the B cell maturation and the antigen specific IgM-IgG switch. In the developing embryo
B cell precursors migrate to the epithelio-mesenchymal rudiment of the BF where they proliferate and diversify their B cell receptor repertoire. In mammals the presence of CXCR4, a receptor for the chemokine stromal cell-derived factor-1 (SDF1, also named CXCL12) mediates migration of leukocytes and hematopoietic progenitors in response to CXCL12. Recent microarray work revealed different expression levels of CXCR4/CXCL12 signaling in developing avian B cells.
Aims: The first aim of this work was to analyze the normal expression pattern of CXCR4 and CXCL12 during development of the BF. To determine whether the CXCR4/CXCL12 signaling mediates migration of avian B cell precursors we have investigated the effect of inhibiting endogenous CXCR4 signaling with AMD3100.
Methods: GFP-chicken chorioallantoic membrane (CAM) assays, in situ hybridization, immunocytochemistry and immunofluorescence technique.
Results: CXCR4 receptor is first expressed by B cell progenitors in the BF at embryonic
day 10 (E10) and show an increasing expression of the receptor from the B cell immigration until hatch. After hatching CXCR4 expression is slowly downregulating from chB6+ medullary B cells. CXCL12 mRNA expression is detected in the BF mesenchyme during all stages of B cell colonization: earliest CXCL12 expression was observed at E10 in the subepithelial mesenchyme. As lymphoid cells colonize the surface epithelium and induce follicle bud formation CXCL12 expression decrease from the mesenchyme and becomes more pronounced inside the developing follicles. Analysis of CAM showed considerable reduction of B cells in follicle buds.
Conclusion: Our results demonstrate that the CXCR4/CXCL12 pathway represent a signiﬁcant signal for the migration of the B cell precursors into the BF primordium and the colonization of the bursal follicles.
Grant NFKI: 124740
Doctoral School: Semmelweis University, Doctoral School of Molecular Medicine
Program: Embryology, Theoretical, Experimental and Clinical Developmental Biology
Supervisor: Nándor Nagy
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