BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Cédric Schleiss, Wassila Ilias, Ouria Tahar, Yonca Güler, Laurent Miguet, Caroline Mayeur-Rousse, Laurent Mauvieux, Luc-Matthieu Fornecker, Elise Toussaint, Raoul Herbrecht, Frédéric Bertrand, Myriam Maumy-Bertrand, Thierry Martin, Sylvie Fournel, Philippe Georgel, Seiamak Bahram, Laurent Vallat

ABSTRACT

A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies. More... »

PAGES

701

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-36853-8

DOI

http://dx.doi.org/10.1038/s41598-018-36853-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111648856

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30679590


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