Identification of a human splenic marginal zone B cell precursor with NOTCH2-dependent differentiation properties

被引：99

作者：

Descatoire, Marc ^{[1
]}

Weller, Sandra ^{[1
]}

Irtan, Sabine ^{[2
]}

Sarnacki, Sabine

Feuillard, Jean ^{[3
,4
]}

Storck, Sebastien ^{[1
]}

Guiochon-Mantel, Anne ^{[5
,6
]}

Bouligand, Jerome ^{[5
,6
]}

Morali, Alain ^{[7
]}

Cohen, Joseph ^{[8
,9
,10
]}

Jacquemin, Emmanuel ^{[8
,9
,10
,11
]}

Iascone, Maria ^{[12
]}

Bole-Feysot, Christine ^{[13
]}

Cagnard, Nicolas ^{[14
]}

Weill, Jean-Claude ^{[1
]}

Reynaud, Claude-Agnes ^{[1
]}

机构：

[1] Univ Paris 05, Sorbonne Paris Cite, CNRS,Fac Med, Inst Necker Enfants Malad,INSERM U1151,UMR 8253, F-75014 Paris, France

[2] Univ Paris 05, Hop Necker Enfants Malad, Serv Chirurg Pediat, F-75015 Paris, France

[3] Fac Med Limoges, CNRS, Unite Mixte Rech 7276, F-887025 Limoges, France

[4] Ctr Hosp Univ Dupuytren, Hematol Lab, F-87042 Limoges, France

[5] Univ Paris 11, Fac Med Paris Sud, INSERM, Unite Mixte Rech S693, F-94276 Le Kremlin Bicetre, France

[6] Hop Bicetre, AP HP, Serv Genet Mol Pharmacogenet & Hormonol, F-94275 Le Kremlin Bicetre, France

[7] CHU Nancy Brabois, Hop Enfants, INSERM, U954, F-54511 Vandoeuvre Les Nancy, France

[8] Hop Bicetre, AP HP, F-94275 Le Kremlin Bicetre, France

[9] Hop Bicetre, AP HP, Ctr Reference Natl Atresie Voies Biliaires, F-94275 Le Kremlin Bicetre, France

[10] Univ Paris 11, F-94275 Le Kremlin Bicetre, France

[11] Univ Paris 11, INSERM, U757, F-91405 Orsay, France

[12] AO Papa Giovanni XXIII, Mol Genet Lab, I-24127 Bergamo, Italy

[13] Hop Necker Enfants Malad, Plateforme Genom Fdn Imagine, F-75015 Paris, France

[14] Univ Paris 05, Plateforme Bioinformat, F-75015 Paris, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 05期

关键词：

IMMUNOGLOBULIN REPERTOIRE; NOTCH2; MUTATIONS; IGM MEMORY; EXPRESSION; POPULATIONS; PATHWAYS; SPLEEN; CD27; DIVERSIFICATION; HYPERMUTATION;

D O I：

10.1084/jem.20132203

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：986 / 1000

页数：15

共 48 条

[1]

Persistence of effector memory Th1 cells is regulated by Hopx [J].