Population B régulatrice dans la leucémie lymphoïde chronique : phénotype et interactions fonctionnelles avec les lymphocytes T en lien avec l’évolutivité

Abstract : Chronic Lymphocytic Leukemia (CLL) is a clonal B cell malignancy of the elderly. This neoplasm is characterized by a heterogeneous clinical course from indolent chronic disease to progressive lymphadenopathy that remains incurable. The aim of my PhD was to undertake a comprehensive phenotypic and functional analysis of the B cell subpopulations responsible for their survival advantage. CLL B cell purification from 30 patients indicate the presence in various extents of leukemic B cell subpopulations producing immune-regulatory cytokines, notably IL-10 and TGFβ1. Remarkably, these CLL subpopulations express the FOXP3 transcription factor, a marker of regulatory T cells. These subpopulations present a phenotypic signature, distinguishable from regulatory B cells populations, with specific markers of activated memory B cells. Functional studies prove their regulatory capacities on T cell differentiation, proliferation and secretion, contributing to the T cell dysfunction observed in CLL. Finally, statistical analysis combining IL-10, TGFβ1 and FOXP3 expressions for these subpopulations allows generating a poly-functional index correlated with two major risk factors of CLL progression. Our data characterize novel CLL B cell subpopulations that are involved in disease progression and give a rational to CLL B cell survival in secondary lymphoid organs.
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Arsène Mekinian. Population B régulatrice dans la leucémie lymphoïde chronique : phénotype et interactions fonctionnelles avec les lymphocytes T en lien avec l’évolutivité. Biologie moléculaire. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCD052⟩. ⟨tel-02272532⟩

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