title: CD24(hi)CD27⁺ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease.
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.
authors.affiliation: 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.
authors.forename: Adèle
authors.initials: A
authors.lastname: de Masson
authors.affiliation: 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.
authors.forename: Jean-David
authors.initials: JD
authors.lastname: Bouaziz
authors.affiliation: 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;
authors.forename: Hélène
authors.initials: H
authors.lastname: Le Buanec
authors.affiliation: Hematology and Transplantation.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Hematology and Transplantation.
authors.forename: Alix
authors.initials: A
authors.lastname: O'Meara
authors.affiliation: Therapeutic Apheresis Unit.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parquet
authors.affiliation: Dermatology Department.
authors.forename: Michel
authors.initials: M
authors.lastname: Rybojad
authors.affiliation: 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;
authors.forename: Estelle
authors.initials: E
authors.lastname: Hau
authors.affiliation: 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;
authors.forename: Jean-Benoît
authors.initials: JB
authors.lastname: Monfort
authors.affiliation: 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;
authors.forename: Mylène
authors.initials: M
authors.lastname: Branchtein
authors.affiliation: Hematology and Transplantation.
authors.forename: David
authors.initials: D
authors.lastname: Michonneau
authors.affiliation: 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;
authors.forename: Valérie
authors.initials: V
authors.lastname: Dessirier
authors.affiliation: Hematology and Transplantation.
authors.forename: Flore
authors.initials: F
authors.lastname: Sicre de Fontbrune
authors.affiliation: Pneumology Department.
authors.forename: Anne
authors.initials: A
authors.lastname: Bergeron
authors.affiliation: Adolescents and Young Adults Hematology Unit, and.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Itzykson
authors.affiliation: Adolescents and Young Adults Hematology Unit, and.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhédin
authors.affiliation: Immunology Department, Saint-Louis Hospital, Paris, France; and.
authors.forename: Djaouida
authors.initials: D
authors.lastname: Bengoufa
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Hematology and Transplantation, INSERM Unité Mixte de Recherche Scientifique 1160, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Hematology and Transplantation.
authors.forename: Aliénor
authors.initials: A
authors.lastname: Xhaard
authors.affiliation: 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.
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.affiliation: 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;
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: University of Paris Diderot, Sorbonne Paris Cité, Paris, France; Hematology and Transplantation, INSERM Unité Mixte de Recherche Scientifique 1160, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism*; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C508609:IL10 protein, human; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1