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

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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Submitted on : Friday, January 23, 2015 - 2:49:40 PM
Last modification on : Friday, May 15, 2020 - 12:22:04 PM
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Michel Jourdan, Maïlys Cren, N. Robert, Karine Bolloré, Thierry Fest, et al.. IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors.. Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2014, 28 (8), pp.1647-56. ⟨10.1038/leu.2014.61⟩. ⟨hal-00974531⟩

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