Format

Send to

Choose Destination
Leukemia. 2014 Aug;28(8):1647-56. doi: 10.1038/leu.2014.61. Epub 2014 Feb 7.

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

Author information

1
INSERM, U1040, Montpellier, France.
2
Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
3
1] Pôle Cellules et Tissus, Centre Hospitalier Universitaire, Rennes, France [2] INSERM, U917, Rennes, France.
4
1] INSERM, U1040, Montpellier, France [2] Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
5
INSERM, U917, Rennes, France.
6
1] Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany [2] Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
7
1] INSERM, U1040, Montpellier, France [2] Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France [3] Université MONTPELLIER1, UFR Médecine, Montpellier, France.

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.

PMID:
24504026
DOI:
10.1038/leu.2014.61
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for HAL archives ouvertes
Loading ...
Support Center