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Immunology

IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors

Leukemia volume 28, pages 1647–1656 (2014)Cite this article

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Abstract

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.

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Acknowledgements

This work was supported by grants from ARC (SL220110603450, Paris, France), from ANR (2012-109/087437), and the European Community (FP7-OVERMYR). We thank Mrs Pantesco from the Microarray Core Facility of IRB (http://irb.montp.inserm.fr/en/index.php?page=Plateau&IdEquipe=6), Dr Duperray from the cytometry platform of IRB (http://irb.montp.inserm.fr/en/index.php?page=Plateau&IdEquipe=3, Montpellier Rio Imaging) and Dr Reme from the IRB Bioinformatics platform (http://irb.montp.inserm.fr/en/index.php?page=Plateau&IdEquipe=18).

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Authors and Affiliations

  1. INSERM, U1040, Montpellier, France

    M Jourdan, M Cren, C Duperray & B Klein

  2. Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France

    N Robert, K Bolloré, C Duperray & B Klein

  3. Pôle Cellules et Tissus, Centre Hospitalier Universitaire, Rennes, France

    T Fest & K Tarte

  4. INSERM, U917, Rennes, France

    T Fest, F Guilloton & K Tarte

  5. Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany

    D Hose

  6. Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany

    D Hose

  7. Université MONTPELLIER1, UFR Médecine, Montpellier, France

    B Klein

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  1. M Jourdan
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Correspondence to B Klein.

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Author contributions

MJ designed the research, performed the experiments and wrote the paper. KT, TF and FG, provided SCs and corrected the paper. MC, NR and KB performed the experiments. CD provided assistance for cytometry experiments. DH provided the data of gene-expression profiling of BMPCs. BK is the senior investigator who designed research and wrote the paper.

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Jourdan, M., Cren, M., Robert, N. et al. IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors. Leukemia 28, 1647–1656 (2014). https://doi.org/10.1038/leu.2014.61

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