title: 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.
authors: INSERM, U1040, Montpellier, France.
authors: M
authors: M
authors: Jourdan
authors: INSERM, U1040, Montpellier, France.
authors: M
authors: M
authors: Cren
authors: Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
authors: N
authors: N
authors: Robert
authors: Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
authors: K
authors: K
authors: Bolloré
authors: 1] Pôle Cellules et Tissus, Centre Hospitalier Universitaire, Rennes, France [2] INSERM, U917, Rennes, France.
authors: T
authors: T
authors: Fest
authors: 1] INSERM, U1040, Montpellier, France [2] Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
authors: C
authors: C
authors: Duperray
authors: INSERM, U917, Rennes, France.
authors: F
authors: F
authors: Guilloton
authors: 1] Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany [2] Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors: D
authors: D
authors: Hose
authors: 1] Pôle Cellules et Tissus, Centre Hospitalier Universitaire, Rennes, France [2] INSERM, U917, Rennes, France.
authors: K
authors: K
authors: Tarte
authors: 1] INSERM, U1040, Montpellier, France [2] Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France [3] Université MONTPELLIER1, UFR Médecine, Montpellier, France.
authors: B
authors: B
authors: Klein
mesh_terms: D053265:B-Cell Activation Factor Receptor / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology; D010950:Plasma Cells / Q000187:drug effects* / Q000502:physiology; D059467:Transcriptome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000494:pharmacology*
chemical_list: D053265:B-Cell Activation Factor Receptor; D054377:Chemokine CXCL12; D015850:Interleukin-6; D016328:NF-kappa B; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13