Transcriptome analysis identifies CCR7 and cell adhesion molecules as mediators of B cell migration to the bursa of Fabricius during chicken embryonic development
Status In-Process Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články
PubMed
40461995
PubMed Central
PMC12131466
DOI
10.1186/s12864-025-11749-w
PII: 10.1186/s12864-025-11749-w
Knihovny.cz E-zdroje
- Klíčová slova
- Adaptive immunity, B cell development, B cell migration, Bursa of Fabricius, Cell adhesion molecules, Chicken embryonic development, Transcriptomics,
- Publikační typ
- časopisecké články MeSH
UNLABELLED: The development of functional B lymphocytes during chicken embryogenesis relies on a series of tightly regulated processes. Precursor B cells migrate from the spleen via the blood to the bursa of Fabricius, where they colonize the bursal follicles to undergo further maturation and differentiation. To better understand the molecular mechanisms underlying early B cell migration in the chicken embryo, transcriptome analysis of B cells isolated from the spleen, blood, and bursa at embryonic days (ED) 12, ED14, and ED16 was performed. These findings suggest that sphingosine-1-phosphate (S1P) and its receptors regulate B cell presence in the bloodstream, while CCR7 and CXCR4 guide B cells to the bursa. Additionally, integrins and cell adhesion molecules, such as PECAM1, appear to facilitate transendothelial migration into the bursal mesenchyme. This study highlights a coordinated interplay between chemokines, integrins and cell adhesion molecules involved in B cell recruitment and colonization of the bursa microenvironment. These findings enhance our understanding of early B cell migration and shed light on the mechanisms governing B cell trafficking during chicken embryonic development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-025-11749-w.
Center for Infection Prevention Technical University of Munich Freising Germany
Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic
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Houssaint E, Mansikka A, Vainio O. Early separation of B and T lymphocyte precursors in chick embryo. J Exp Med. 1991;174(2):397–406. PubMed PMC
Dieterlen-Lievre F. On the origin of Haemopoietic stem cells in the avian embryo: an experimental approach. J Embryol Exp Morphol. 1975;33(3):607–19. PubMed
Le Douarin NM, Houssaint E, Jotereau FV, Belo M. Origin of Hemopoietic stem cells in embryonic bursa of Fabricius and bone marrow studied through interspecific chimeras. Proc Natl Acad Sci U S A. 1975;72(7):2701–5. PubMed PMC
Benatar T, Iacampo S, Tkalec L, Ratcliffe MJ. Expression of Immunoglobulin genes in the avian embryo bone marrow revealed by retroviral transformation. Eur J Immunol. 1991;21(10):2529–36. PubMed
Pink JR, Vainio O, Rijnbeek AM. Clones of B lymphocytes in individual follicles of the bursa of Fabricius. Eur J Immunol. 1985;15(1):83–7. PubMed
Cooper MD, Peterson RD, Good RA. Delineation of the thymic and bursal lymphoid systems in the chicken. Nature. 1965;205:143–6. PubMed
Ratcliffe MJ. Antibodies, Immunoglobulin genes and the bursa of Fabricius in chicken B cell development. Dev Comp Immunol. 2006;30(1–2):101–18. PubMed
Weill JC, Reynaud CA. The chicken B cell compartment. Science. 1987;238(4830):1094–8. PubMed
McCormack WT, Tjoelker LW, Thompson CB. Immunoglobulin gene diversification by gene conversion. Prog Nucleic Acid Res Mol Biol. 1993;45:27–45. PubMed
Reynaud CA, Bertocci B, Dahan A, Weill JC. Formation of the chicken B-cell repertoire: ontogenesis, regulation of Ig gene rearrangement, and diversification by gene conversion. Adv Immunol. 1994;57:353–78. PubMed
Lassila O. Emigration of B cells from chicken bursa of Fabricius. Eur J Immunol. 1989;19(5):955–8. PubMed
Reynaud CA, Imhof BA, Anquez V, Weill JC. Emergence of committed B lymphoid progenitors in the developing chicken embryo. EMBO J. 1992;11(12):4349–58. PubMed PMC
Pickel JM, McCormack WT, Chen CH, Cooper MD, Thompson CB. Differential regulation of V(D)J recombination during development of avian B and T cells. Int Immunol. 1993;5(8):919–27. PubMed
Sayegh CE, Ratcliffe MJ. Perinatal deletion of B cells expressing surface Ig molecules that lack V(D)J-encoded determinants in the bursa of Fabricius is not due to intrafollicular competition. J Immunol. 2000;164(10):5041–8. PubMed
Schusser B, Collarini EJ, Yi H, Izquierdo SM, Fesler J, Pedersen D, et al. Immunoglobulin knockout chickens via efficient homologous recombination in primordial germ cells. Proc Natl Acad Sci U S A. 2013;110(50):20170–5. PubMed PMC
Nagy N, Busalt F, Halasy V, Kohn M, Schmieder S, Fejszak N, et al. In and out of the Bursa-The role of CXCR4 in chicken B cell development. Front Immunol. 2020;11:1468. PubMed PMC
Laparidou M, Schlickenrieder A, Thoma T, Lengyel K, Schusser B. Blocking of the CXCR4-CXCL12 interaction inhibits the migration of chicken B cells into the Bursa of Fabricius. Front Immunol. 2019;10:3057. PubMed PMC
Sayegh CE, Demaries SL, Iacampo S, Ratcliffe MJ. Development of B cells expressing surface Immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius. Proc Natl Acad Sci U S A. 1999;96(19):10806–11. PubMed PMC
Fonfria J, Moreno J, Gomez del Moral M, Alonso L, Zapata AG. The diffusely-infiltrated lymphoid tissue of the bursa of Fabricius of Sturnus unicolor. Histological organization and functional significance. Histol Histopathol. 1994;9(2):333–8. PubMed
Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994;76(2):301–14. PubMed
Fabbri M, Bianchi E, Fumagalli L, Pardi R. Regulation of lymphocyte traffic by adhesion molecules. Inflamm Res. 1999;48(5):239–46. PubMed
Sinha RK, Mage RG. Developing neonatal rabbit appendix, a primary lymphoid organ, is seeded by immature blood-borne B cells: evidence for roles for CD62L/PNAd, CCR7/CCL21, alpha4beta1 and LFA-1. Dev Comp Immunol. 2004;28(7–8):829–41. PubMed
Masteller EL, Lee KP, Carlson LM, Thompson CB. Expression of Sialyl Lewis(x) and Lewis(x) defines distinct stages of chicken B cell maturation. J Immunol. 1995;155(12):5550–6. PubMed
Lasky LA. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992;258(5084):964–9. PubMed
Palojoki E, Jalkanen S, Toivanen P. Sialyl LewisX carbohydrate is expressed differentially during avian lymphoid cell development. Eur J Immunol. 1995;25(9):2544–50. PubMed
Sinha RK, Alexander C, Mage RG. Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix. Vet Immunol Immunopathol. 2006;110(1–2):97–108. PubMed
Chatzikonstantinou S, Poulidou V, Arnaoutoglou M, Kazis D, Heliopoulos I, Grigoriadis N et al. Signaling through the S1P-S1PR Axis in the gut, the immune and the central nervous system in multiple sclerosis: implication for pathogenesis and treatment. Cells. 2021;10(11). PubMed PMC
Sic H, Kraus H, Madl J, Flittner KA, von Munchow AL, Pieper K, et al. Sphingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis. J Allergy Clin Immunol. 2014;134(2):420–8. PubMed
Juarez JG, Harun N, Thien M, Welschinger R, Baraz R, Pena AD, et al. Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice. Blood. 2012;119(3):707–16. PubMed
Crousillac S, Colonna J, McMains E, Dewey JS, Gleason E. Sphingosine-1-phosphate elicits receptor-dependent calcium signaling in retinal Amacrine cells. J Neurophysiol. 2009;102(6):3295–309. PubMed PMC
Bradaric MJ, Barua A, Penumatsa K, Yi Y, Edassery SL, Sharma S, et al. Sphingosine-1 phosphate receptor (S1p1), a critical receptor controlling human lymphocyte trafficking, is expressed in Hen and human ovaries and ovarian tumors. J Ovarian Res. 2011;4(1):4. PubMed PMC
Wilson SM, Chambers AF. Experimental metastasis assays in the chick embryo. Curr Protoc Cell Biol. 2004;Chap. 19:Unit 19 6. PubMed
Cossarizza A, Chang HD, Radbruch A, Akdis M, Andra I, Annunziato F, et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies. Eur J Immunol. 2017;47(10):1584–797. PubMed PMC
Andrews S. FastQC 2010 [Available from: https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Ewels P, Magnusson M, Lundin S, Kaller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32(19):3047–8. PubMed PMC
Chen S, Zhou Y, Chen Y, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34(17):i884–90. PubMed PMC
Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019;37(8):907–15. PubMed PMC
Liao Y, Smyth GK, Shi W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30(7):923–30. PubMed
Love MI, Huber W, Anders S. Moderated Estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. PubMed PMC
Galaxy C. The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update. Nucleic Acids Res. 2022;50(W1):W345–51. PubMed PMC
Kucukural A, Yukselen O, Ozata DM, Moore MJ, Garber M. DEBrowser: interactive differential expression analysis and visualization tool for count data. BMC Genomics. 2019;20(1):6. PubMed PMC
Heberle H, Meirelles GV, da Silva FR, Telles GP, Minghim R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 2015;16(1):169. PubMed PMC
Institute B. Morpheus [RRID: SCR_017386:[Available from: https://software.broadinstitute.org/morpheus
Thomas PD, Ebert D, Muruganujan A, Mushayahama T, Albou LP, Mi H. PANTHER: making genome-scale phylogenetics accessible to all. Protein Sci. 2022;31(1):8–22. PubMed PMC
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504. PubMed PMC
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57. PubMed
Blake JA, Richardson JE, Davisson MT, Eppig JT. The mouse genome database (MGD). A comprehensive public resource of genetic, phenotypic and genomic data. The mouse genome informatics group. Nucleic Acids Res. 1997;25(1):85–91. PubMed PMC
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92. PubMed PMC
Szocs E, Balic A, Soos A, Halasy V, Nagy N. Characterization and ontogeny of a novel lymphoid follicle inducer cell during development of the bursa of Fabricius. Front Immunol. 2024;15:1449117. PubMed PMC
Kothlow S, Morgenroth I, Graef Y, Schneider K, Riehl I, Staeheli P, et al. Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken. Int Immunol. 2007;19(2):203–15. PubMed
Kothlow S, Morgenroth I, Tregaskes CA, Kaspers B, Young JR. CD40 ligand supports the long-term maintenance and differentiation of chicken B cells in culture. Dev Comp Immunol. 2008;32(9):1015–26. PubMed
Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E, et al. CCR7 coordinates the primary immune response by Establishing functional microenvironments in secondary lymphoid organs. Cell. 1999;99(1):23–33. PubMed
Okada T, Ngo VN, Ekland EH, Forster R, Lipp M, Littman DR, et al. Chemokine requirements for B cell entry to lymph nodes and Peyer’s patches. J Exp Med. 2002;196(1):65–75. PubMed PMC
McHeik S, Van Eeckhout N, De Poorter C, Gales C, Parmentier M, Springael JY. Coexpression of CCR7 and CXCR4 during B cell development controls CXCR4 responsiveness and bone marrow homing. Front Immunol. 2019;10:2970. PubMed PMC
Huttenlocher A, Horwitz AR. Integrins in cell migration. Cold Spring Harb Perspect Biol. 2011;3(9):a005074. PubMed PMC
Muller WA, Weigl SA, Deng X, Phillips DM. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993;178(2):449–60. PubMed PMC
Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, et al. Junctional adhesion molecule, a novel member of the Immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol. 1998;142(1):117–27. PubMed PMC
Donate C, Ody C, McKee T, Ruault-Jungblut S, Fischer N, Ropraz P, et al. Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C. Cancer Res. 2013;73(2):640–51. PubMed
Kabashima K, Haynes NM, Xu Y, Nutt SL, Allende ML, Proia RL, et al. Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism. J Exp Med. 2006;203(12):2683–90. PubMed PMC
Allende ML, Tuymetova G, Lee BG, Bonifacino E, Wu YP, Proia RL. S1P1 receptor directs the release of immature B cells from bone marrow into blood. J Exp Med. 2010;207(5):1113–24. PubMed PMC
Ko KH, Lee IK, Kim G, Gu MJ, Kim HY, Park BC, et al. Changes in bursal B cells in chicken during embryonic development and early life after hatching. Sci Rep. 2018;8(1):16905. PubMed PMC