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dc.contributor.authorvon Muenchow, Lilly
dc.contributor.authorTsapogas, Panagiotis
dc.contributor.authorAlbertí-Servera, Llucia
dc.contributor.authorCapoferri, Giuseppina
dc.contributor.authorDoelz, Marianne
dc.contributor.authorRolink, Hannie
dc.contributor.authorBosco, Nabil
dc.contributor.authorCeredig, Rhodri
dc.contributor.authorRolink, Antonius G.
dc.identifier.citationvon Muenchow, L., Tsapogas, P., Albertí-Servera, L., Capoferri, G., Doelz, M., Rolink, H., Bosco, N., Ceredig, R. and Rolink, A. G. (2016), Pro-B cells propagated in stromal cell-free cultures reconstitute functional B-cell compartments in immunodeficient mice. Eur. J. Immunol.. doi:10.1002/eji.201646638en_IE
dc.description.abstractUp to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free cultures supplemented with IL-7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D-J heavy chain genes. Both FL and BM pro-B cells reconstituted the B-cell compartments of immuno-incompetent Rag2-deficient mice, with FL pro-B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro-B cells giving rise mainly to MZB cells. Reconstituted Rag2-deficient mice generated significant levels of IgM and IgG antibodies to a type II T-independent antigen; mice reconstituted with FL pro-B cells generated surprisingly high IgG1 titers. Finally, we show for the first time that mice reconstituted with mixtures of pro-B and pro-T cells propagated in stromal cell-free in vitro cultures mounted a T-cell-dependent antibody response. This novel stromal cell-free culture system facilitates our understanding of B-cell development and might be applied clinically.en_IE
dc.description.sponsorshipA.G.R. is holder of the chair in immunology endowed by L. Hoffmann – La Roche Ltd, Basel. This study was supported by the Swiss National Science Foundation. This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 315902. One author (Lilly von Muenchow) gratefully acknowledges receipt of a Marie Curie Research Fellowship. Antonius G. Rolink and Rhodri Ceredig are Partners within the Marie Curie Initial Training Network DECIDE (Decision-making within cells and differentiation entity therapies). R.C. was supported by Science Foundation Ireland under grant numbers SFI09/SRC/B1794 and SFI07/SK/B1233b. We would like to thank the members of the DBM-Microscopy Core Facility for their continuous support.en_IE
dc.relation.ispartofEuropean Journal Of Immunologyen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectPro-B cellsen_IE
dc.subjectStromal cell-free culturesen_IE
dc.subjectB-cell compartmentsen_IE
dc.subjectImmunodeficient miceen_IE
dc.titlePro-B cells propagated in stromal cell-free cultures reconstitute functional B-cell compartments in immunodeficient miceen_IE
dc.local.contactRhodri Ceredig, Room 217, Orbsen Building, Nui Galway. 5916 Email:

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