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TLR9 Ligand Induces the Generation of CD20+ Plasmablasts and Plasma Cells from CD27+ Memory B-Cells

Abstract : Plasma cells (PCs) have a heterogeneous phenotype in humans. While bone marrow PCsare CD20−CD138+, tonsil PCs are CD20+CD138+/−and peripheral plasmablasts (PBs)are CD20−CD138−.In vitro, PCs are mainly generated by the activation of CD27+mem-ory B-cells through transient stimulation of CD40, and their phenotype appears similarto that of bone marrow PCs. While CD20 expression is lost at the plasmablastic stage,CD138 expression appears only at the PC stage. Thus, the CD20+CD138±phenotype oftonsil PCs does not represent an intermediate stage in the differentiation of memory B-cells into PCs. Because it has been previously shown that TLR9 activation was more ablethan CD40 stimulation to induce the differentiation of IgM+CD27+B-cells, we wonderedwhether TLR9 or CD40 stimulation would induce the same phenotype of PCs. Thus, wecompared the differentiation of CD27+B-cells isolated from either the tonsils or periph-eral blood and stimulated with either CD40L-expressing fibroblasts or a TLR9 ligand, CpGoligodeoxynucleotide (CpG ODN). We observed that CpG ODN mainly induced CD27+B-cell differentiation into CD20+CD38+CD138−PBs and CD20+CD38+CD138±PCs, whichappear similar to tonsil PCs. Removal of CpG ODN during differentiation induced a decreasein the CD20+plasmablastic population, and, conversely, stimulation of CD40L-induced pre-plasmablasts with CpG ODN increased the population of CD20+CD38+PBs. Analysis ofIg secretion showed that CpG ODN induced increased IgM secretion compared to CD40L.PCs from patients with multiple myeloma, the malignant counterpart of bone marrow PCs,rarely express CD20. We show that CpG ODN did not induce or increase CD20 in nineIgG or IgA myeloma cell lines. These data strongly suggest that CpG ODN mainly targetsCD27 IgM B-cells.
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https://www.hal.inserm.fr/inserm-03290331
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Submitted on : Monday, July 19, 2021 - 12:16:12 PM
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Alexandrine Geffroy-Luseau, David Chiron, Géraldine Descamps, Gaëtan Jégo, Martine Amiot, et al.. TLR9 Ligand Induces the Generation of CD20+ Plasmablasts and Plasma Cells from CD27+ Memory B-Cells. Frontiers in Immunology, Frontiers, 2011, 2, ⟨10.3389/fimmu.2011.00083⟩. ⟨inserm-03290331⟩

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