CD24(hi)CD27⁺ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease.

Fiche publication


Date publication

mars 2015

Journal

Blood

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BENSUSSAN Armand


Tous les auteurs :
de Masson A, Bouaziz JD, Le Buanec H, Robin M, O'Meara A, Parquet N, Rybojad M, Hau E, Monfort JB, Branchtein M, Michonneau D, Dessirier V, Sicre de Fontbrune F, Bergeron A, Itzykson R, Dhédin N, Bengoufa D, Peffault de Latour R, Xhaard A, Bagot M, Bensussan A, Socié G

Résumé

Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma cells has been described in mice. Dysfunction of B cells that maintain homeostasis may play a role in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+) and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10-producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10-producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast frequencies but decreased IL-10-producing plasmablasts. These results suggest a role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD.

Mots clés

ADP-ribosyl Cyclase 1, metabolism, Adult, Aged, Animals, B-Lymphocytes, Regulatory, immunology, CD24 Antigen, metabolism, Cell Differentiation, Chronic Disease, Female, Graft vs Host Disease, etiology, Hematopoietic Stem Cell Transplantation, adverse effects, Humans, Interleukin-10, biosynthesis, MAP Kinase Signaling System, Male, Membrane Glycoproteins, metabolism, Mice, Middle Aged, Plasma Cells, immunology, Prospective Studies, STAT3 Transcription Factor, metabolism, Signal Transduction, Tumor Necrosis Factor Receptor Superfamily, Member 7, metabolism, Young Adult

Référence

Blood. 2015 03 12;125(11):1830-9