IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors
| Autor: | Thierry Fest, Fabien Guilloton, Dirk Hose, Nicolas Robert, Karin Tarte, Maïlys Cren, Karine Bollore, Bernard Klein, Michel Jourdan, Christophe Duperray |
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| Přispěvatelé: | Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Medizinische KlinikV, Universitätklinikum Heidelberg, Department of Internal Medicine V, Universität Heidelberg [Heidelberg] = Heidelberg University-Universität Heidelberg [Heidelberg] = Heidelberg University-National Center for Tumor Diseases (NCTD), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universität Heidelberg [Heidelberg]-Universität Heidelberg [Heidelberg]-National Center for Tumor Diseases (NCTD), Universität Heidelberg [Heidelberg] |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Stromal cell Cell Survival Cellular differentiation [SDV]Life Sciences [q-bio] Plasma Cells Tumor Necrosis Factor Ligand Superfamily Member 13 MESH: B-Cell Activation Factor Receptor/pharmacology Cell Survival Cells Cultured Chemokine CXCL12/pharmacology* Humans Interleukin-6/pharmacology* NF-kappa B/physiology Plasma Cells/drug effects* Plasma Cells/physiology Transcriptome Tumor Necrosis Factor Ligand Superfamily Member 13/pharmacology Plasma cell Biology 03 medical and health sciences 0302 clinical medicine medicine Humans Cells Cultured 030304 developmental biology 0303 health sciences Interleukin-6 NF-kappa B Hematology Cell cycle Chemokine CXCL12 In vitro Cell biology Haematopoiesis medicine.anatomical_structure Oncology Immunology biology.protein Antibody Stem cell Transcriptome B-Cell Activation Factor Receptor 030215 immunology |
| Zdroj: | Leukemia Leukemia, 2014, 28 (8), pp.1647-56. ⟨10.1038/leu.2014.61⟩ Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2014, 28 (8), pp.1647-56. ⟨10.1038/leu.2014.61⟩ |
| ISSN: | 0887-6924 1476-5551 |
| DOI: | 10.1038/leu.2014.61⟩ |
| Popis: | International audience; The recent understanding of plasma cell (PC) biology has been obtained mainly from murine models. The current concept is that plasmablasts home to the BM and further differentiate into long-lived PCs (LLPCs). These LLPCs survive for months in contact with a complex niche comprising stromal cells (SCs) and hematopoietic cells, both producing recruitment and survival factors. Using a multi-step culture system, we show here the possibility to differentiate human memory B cells into LLPCs surviving for at least 4 months in vitro and producing immunoglobulins continuously. A remarkable feature is that IL-6 is mandatory to generate LLPCs in vitro together with either APRIL or soluble factors produced by SCs, unrelated to APRIL/BAFF, SDF-1, or IGF-1. These LLPCs are out of the cell cycle, express highly PC transcription factors and surface markers. This model shows a remarkable robustness of human LLPCs, which can survive and produce highly immunoglobulins for months in vitro without the contact with niche cells, providing the presence of a minimal cocktail of growth factors and nutrients. This model should be useful to understand further normal PC biology and its deregulation in premalignant or malignant PC disorders. |
| Databáze: | OpenAIRE |
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