Mesenchymal stem cells suppress B-cell terminal differentiation.

Mesenchymal stem cells suppress B-cell terminal differentiation.
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DOI:
10.1016/j.exphem.2009.01.005
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发表时间:
2009-05
影响因子:
2.6
通讯作者:
Mullen, Yoko
Mullen, Yoko
中科院分区:
医学4区
文献类型:
--
作者:
Asari, Sadaki;Itakura, Shin;Ferreri, Kevin;Liu, Chih-Pin;Kuroda, Yoshikazu;Kandeel, Fouad;Mullen, Yoko

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间充质干细胞(MSC)已被证明对多种免疫细胞谱系具有免疫调节特性。然而,它们对B淋巴细胞的影响仍不清楚。我们研究了间充质干细胞对B细胞调节的作用,特别强调了间充质干细胞体液因子介导的基因调控。从C57 BL/6骨髓中分离MSC并在培养中扩增。脾B细胞用抗CD 43抗体和免疫磁珠纯化。将B细胞和MSC在transwell系统的单独隔室中共培养。对于B细胞刺激,在体外使用脂多糖(LPS),在体内使用T依赖性和T非依赖性抗原。在MSC共培养物中,LPS刺激的B细胞增殖被抑制,CD 138+细胞百分比降低,并且凋亡的CD 138+细胞的数量减少。在B/MSC共培养中,IgM+细胞百分比高于对照,并且在培养基中释放的IgM量低于对照。在整个3天的培养期间,共培养物中的Blimp-1 mRNA表达受到抑制。来源于MSC培养物的条件培养基在体外阻止了B细胞的终末分化,并且在体内显著抑制了用T细胞非依赖性抗原以及T细胞依赖性抗原免疫的小鼠中的抗原特异性IgM和IgG 1分泌。结果表明,MSC释放的体液因子对B细胞终末分化具有抑制作用。这种抑制可能是通过抑制Blimp-1的表达来介导的,但该因子的性质尚未确定。
Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties on a diverse array of immune cell lineages. However, their effect on B-lymphocytes has remained unclear. We investigated the effect of MSCs on B cell modulation with a special emphasis on gene regulation mediated by MSC humoral factors. MSCs were isolated from C57BL/6 bone marrow and expanded in culture. Splenic B cells were purified using anti-CD43 antibody and immunomagnetic beads. B cells and MSCs were co-cultured in separate compartments in a transwell system. For B cell stimulation, lipopolysaccharide (LPS) was used in vitro and T-dependent and T-independent antigens were used in vivo. In MSC co-cultures, LPS-stimulated B cell proliferation was suppressed, CD138+ cell percentage decreased, and the number of apoptotic CD138+ cells decreased. In the B/MSC co-culture, the IgM+ cell percentage was higher and the IgM amount released in the medium was lower than in the control. The Blimp-1 mRNA expression in the co-culture was suppressed throughout the 3 day culture period. Conditioned media derived from MSC cultures prevented the terminal differentiation of B cells in vitro and significantly suppressed the antigen specific IgM and IgG1 secretion in mice immunized with T cell-independent as well as T cell-dependent antigens in vivo. Results indicate that humoral factor(s) released by MSCs exert a suppressive effect on the B cell terminal differentiation. The suppression may be mediated through inhibition of Blimp-1 expression, but the nature of the factor(s) is yet to be determined.
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