Cette étude a permis l’amélioration de la différenciation in vitro des lymphocytes B mémoires humains suite à leur expansion. Elle a également permis la caractérisation des plasmocytes générés et mis en lumière des éléments de la biologie de ces cellules centrales du système immunitaire humorale. Ces éléments tels que la réponse intracellulaire des plasmocytes générés peuvent permettre une comparaison de ces derniers avec les myélomes multiples et mener à une meilleure compréhension de cette maladie.
Nous avons pu constater que les interactions cellulaires entre CD27 et CD70 et entre CD40 et CD154 sont toutes deux importantes pour la différenciation de lymphocytes B mémoires in vitro. L’ensemble des résultats met en lumière un nouveau modèle intéressant pour la génération de plasmocytes en culture, soit l’activation et l’expansion cellulaire en présence de l’interaction CD154, leur différenciation rapide en précurseurs de plasmocytes avec l’interaction CD70. Nos observations indiquent toutefois que le microenvironnement actuel n’est pas adéquat pour la survie à long-terme. Les plasmocytes CD38hi générés pourraient donc être isolés et
mis dans un milieu de survie constitué de cellules stromales tel qu’illustré à la figure 7.1. Dans un tel contexte, les cellules pourraient devenir aptes à répondre aux molécules de survie telles qu’APRIL ou le CXCL12. D’ailleurs, l’utilisation de telles cellules-support a déjà fait ses preuves dans des systèmes de culture de lymphocytes B [92][132]. Ce modèle permettrait l’obtention de plasmocytes qui pourront par la suite être utilisés pour des patients immunosupprimés, en attendant la reconstitution de leur système immunitaire suite à une transplantation de cellules souches.
Figure 7.1 Modèle proposé pour l’évolution de la différenciation des lymphocytes B mémoires en plasmocytes in vitro. La première phase de la culture consiste en l’activation et l’expansion des lymphocytes
B en utilisant l’interaction CD40-CD154. La deuxième phase en interaction CD27-CD70 induit la différenciation cellulaire tandis que la troisième permet la survie des plasmocytes générés à travers l’interaction de ces cellules avec une lignée stromale. L’expression du marqueur CD31 débute avec la différenciation des lymphocytes B mémoires tandis que le CD39 est présent sur les cellules depuis leur mise en culture. Son expression diminue dans l’environnement de survie des plasmocytes sans toutefois disparaître complètement.
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