title: Identification of a human splenic marginal zone B cell precursor with NOTCH2-dependent differentiation properties.
abstract: Mouse splenic marginal zone precursors (MZPs) differentiate into marginal zone B (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like 1 ligand (Dll1). We report the identification of an MZP subset in the spleen of young children. These MZPs differentiate into MZ-like B cells in vitro in the presence of OP9 cells expressing human DLL1, as demonstrated by the up-regulation of classical MZB cell markers. A set of diagnostic genes discriminating IgM(+)IgD(+)CD27(+) blood and splenic MZB cells from switched B cells was identified (up-regulation of SOX7, down-regulation of TOX, COCH, and HOPX), and their expression during the induction assay mirrored the one of MZB cells. Moreover, Alagille patients with a NOTCH2 haploinsufficiency display a marked reduction of IgM(+)IgD(+)CD27(+) B cells in blood, whereas their switched memory B cells are not affected. Altogether, these results argue in favor of the existence of a rodent-like MZB cell lineage in humans.
authors.affiliation: Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, 75014 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Descatoire
authors.forename: Sandra
authors.initials: S
authors.lastname: Weller
authors.forename: Sabine
authors.initials: S
authors.lastname: Irtan
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.forename: Sébastien
authors.initials: S
authors.lastname: Storck
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.forename: Alain
authors.initials: A
authors.lastname: Morali
authors.forename: Joseph
authors.initials: J
authors.lastname: Cohen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
authors.forename: Maria
authors.initials: M
authors.lastname: Iascone
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cagnard
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
mesh_terms: D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D046228:Microarray Analysis; D008856:Microscopy, Fluorescence; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051883:Receptor, Notch2 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2
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