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Blood. 2015 Mar 12;125(11):1830-9. doi: 10.1182/blood-2014-09-599159. Epub 2015 Jan 20.

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

Author information

1
Laboratory of Oncodermatology, Immunology and Cutaneous Stem Cells, INSERM Unité Mixte de Recherche Scientifique 976, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Dermatology Department.
2
Laboratory of Oncodermatology, Immunology and Cutaneous Stem Cells, INSERM Unité Mixte de Recherche Scientifique 976, Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Paris, France;
3
Hematology and Transplantation.
4
Therapeutic Apheresis Unit.
5
Dermatology Department.
6
Pneumology Department.
7
Adolescents and Young Adults Hematology Unit, and.
8
Immunology Department, Saint-Louis Hospital, Paris, France; and.
9
University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Hematology and Transplantation, INSERM Unité Mixte de Recherche Scientifique 1160, Paris, France.

Abstract

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.

PMID:
25605369
DOI:
10.1182/blood-2014-09-599159
[Indexed for MEDLINE]
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