Journal Article

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

Duperray, C, Fest, T, Bolloré, K, Tarte, K, Klein, B, Cren, M, Hose, D, Jourdan, M, Robert, N, Guilloton, F

2014

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Springer Nature
• Subject: 631/250/1619/40/1742 / 631/45/127/1213 / 692/699/67/1990 / Animal models / APRIL protein / B-Cell Activation Factor Receptor - pharmacology / 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 / Biology / BLyS protein / Bone marrow / Cancer Research / Cell culture / Cell cycle / Cell differentiation / Cell Survival / Cells, Cultured / Chemokine CXCL12 - pharmacology / Critical Care Medicine / Deregulation / Genetic aspects / Growth factors / Hematology / Heparan sulfate / Humans / Immunoglobulins / Immunological memory / Insulin-like growth factor I / Intensive / Interleukin 6 / Interleukin-6 - pharmacology / Internal Medicine / Leukemia / Life Sciences / Lymphocytes B / Medicine / Medicine & Public Health / Memory cells / NF-kappa B - physiology / Nutrients / Oncology / original-article / Plasma / Plasma cells / Plasma Cells - drug effects / Plasma Cells - physiology / Properties / R&D / Research & development / SDF-1 protein / Stromal cells / Surface markers / Survival / Transcription factors / Transcriptome / Tumor Necrosis Factor Ligand Superfamily Member 13 - pharmacology