Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, 75014 Paris, France.
J Exp Med. 2014 May 5;211(5):987-1000. doi: 10.1084/jem.20132203. Epub 2014 Apr 14.
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.
小鼠脾脏边缘区前体细胞（MZPs）在涉及 Notch2 及其配体 delta 样配体 1 配体（Dll1）的信号通路下分化为边缘区 B（MZB）细胞。我们报告了在幼儿脾脏中鉴定出的一个 MZP 亚群。这些 MZPs 在表达人 DLL1 的 OP9 细胞存在下体外分化为 MZ 样 B 细胞，这通过上调经典 MZB 细胞标志物来证明。一组诊断基因被鉴定出来，可以区分 IgM(+)IgD(+)CD27(+)血液和脾脏 MZB 细胞与转换 B 细胞（上调 SOX7，下调 TOX、COCH 和 HOPX），并且它们在诱导试验中的表达反映了 MZB 细胞的表达。此外，具有 NOTCH2 杂合不足的 Alagille 患者血液中 IgM(+)IgD(+)CD27(+)B 细胞明显减少，而其转换记忆 B 细胞不受影响。总之，这些结果支持在人类中存在类似于啮齿动物的 MZB 细胞谱系。
