Functional characterization of B lymphocytes generated <i>in vitro</i> from embryonic stem cells

作     者：Cho, SK Webber, TD Carlyle, JR Nakano, T Lewis, SM Zúñiga-Pflücker, JC 

作者机构：Univ Toronto Dept Immunol Toronto ON M5S 1A8 Canada Osaka Univ Microbial Dis Res Inst Dept Mol Cell Biol Suita Osaka 565 Japan Hosp Sick Children Program Genet & Genom Biol Res Inst Toronto ON M5G 1X8 Canada 

出 版 物：《PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA》 (美国国家科学院汇刊)

年 卷 期：1999年第96卷第17期

页      面：9797-9802页

核心收录：

学科分类：07[理学] 08[工学] 

主　　题：Abelson鼠白血病病毒 B淋巴细胞/生理学 细胞分化/药物作用 共同培养技术 基因重排 B淋巴细胞 血细胞生成 造血干细胞/药物作用 造血干细胞/生理学 配体 膜蛋白质类/药理学 聚合酶链反应 动物 小鼠 

摘      要：To study molecular events involved in B lymphocyte development and V(D)J rearrangement, we have established an efficient system for the differentiation of embryonic stem (ES) cells into mature Ig-secreting B lymphocytes. Here, we show that B lineage cells generated in vitro from ES cells are functionally analogous to normal fetal liver-derived or bone marrow-derived B lineage cells at three important developmental stages: first, they respond to Flt-3 ligand during an early lymphopoietic progenitor stage;second, they become targets for Abelson murine leukemia virus (A-MuLV) infection at a pre-B cell stage;third, they secrete Ig upon stimulation with lipopolysaccharide at a mature mitogen-responsive stage. Moreover, the ES cell-derived A-MuLV-transformed pre-B (EAB) cells are phenotypically and functionally indistinguishable from standard A-MuLV-transformed pre-B cells derived from infection of mouse fetal liver or bone marrow. Notably, EAB cells possess functional V(D)J recombinase activity. In particular, the generation of A-MuLV transformants from ES cells will provide an advantageous system to investigate genetic modifications that will help to elucidate molecular mechanisms in V(D)J recombination and in A-MuLV-mediated transformation.