Pro‐B cells propagated in stromal cell‐free cultures reconstitute functional B‐cell compartments in immunodeficient mice |
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| Authors: | Lilly von Muenchow Panagiotis Tsapogas Llucia Albertí‐Servera Giuseppina Capoferri Marianne Doelz Hannie Rolink Nabil Bosco Rhodri Ceredig Antonius G. Rolink |
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| Affiliation: | 1. Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland;2. Molecular Immune Regulation, Department of Biomedicine, University of Basel, Basel, Switzerland;3. Discipline of Physiology, National University of Ireland, Galway |
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| Abstract: | Up 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. |
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| Keywords: | B cells Bone marrow Cell development Fetal liver Stroma Transplantation |
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