Improved B cell development in humanized NOD-scid IL2Rγ(null) mice transgenically expressing human stem cell factor, granulocyte-macrophage colony-stimulating factor and interleukin-3.
Improved B cell development in humanized NOD-scid IL2Rγ(null) mice transgenically expressing human stem cell factor, granulocyte-macrophage colony-stimulating factor and interleukin-3.
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DOI：
10.1002/iid3.124
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发表时间：
2016-12
影响因子：
3.2
通讯作者：
Brehm, Michael A
中科院分区：
文献类型：
--
作者：
Jangalwe, Sonal;Shultz, Leonard D;Mathew, Anuja;Brehm, Michael A
植入人类免疫系统的免疫缺陷小鼠支持人类造血和对人类特异性病原体的免疫反应的研究。然而，这些人源化小鼠模型的一个显着局限性是，人类 B 细胞在感染或免疫后进行类别转换和产生抗原特异性 IgG 的能力受到严重限制。在这项研究中，我们表征了转基因表达人类干细胞因子（SCF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和IL-3（NSG-SGM3）的NOD-scid IL2Rγnull（NSG）小鼠中植入人类造血干细胞、自体胎儿肝脏和胚胎后人类B细胞的发育和功能。 胸腺组织（骨髓、肝脏、胸腺或 BLT 模型）。 NSG-SGM3 BLT 小鼠快速植入人类免疫细胞并发育出 T 细胞、B 细胞和骨髓细胞。与 NSG BLT 小鼠相比，NSG-SGM3 BLT 小鼠中发育的人类 B 细胞比例较高，具有成熟/幼稚表型，未成熟/过渡型人类 B 细胞相应减少。此外，与 NSG BLT 小鼠相比，NSG-SGM3 BLT 小鼠具有更高的人 IgM 和 IgG 基础水平。此外，NSG-SGM3 BLT 小鼠的登革热病毒感染产生了更高水平的抗原特异性 IgM 和 IgG，而在 NSG BLT 小鼠中未观察到这一结果。我们的研究表明 NSG-SGM3 BLT 小鼠表现出改善的人类 B 细胞发育，并允许产生针对病毒感染的抗原特异性抗体反应。
Immunodeficient mice engrafted with human immune systems support studies of human hematopoiesis and the immune response to human‐specific pathogens. A significant limitation of these humanized mouse models is, however, a severely restricted ability of human B cells to undergo class switching and produce antigen‐specific IgG after infection or immunization. In this study, we have characterized the development and function of human B cells in NOD‐scid IL2Rγnull (NSG) mice transgenically expressing human stem cell factor (SCF), granulocyte macrophage colony‐stimulating factor (GM‐CSF), and IL‐3 (NSG‐SGM3) following engraftment with human hematopoietic stem cells, autologous fetal liver, and thymic tissues (bone marrow, liver, thymus or BLT model). The NSG‐SGM3 BLT mice engraft rapidly with human immune cells and develop T cells, B cells, and myeloid cells. A higher proportion of human B cells developing in NSG‐SGM3 BLT mice had a mature/naive phenotype with a corresponding decrease in immature/transitional human B cells as compared to NSG BLT mice. In addition, NSG‐SGM3 BLT mice have higher basal levels of human IgM and IgG as compared with NSG BLT mice. Moreover, dengue virus infection of NSG‐SGM3 BLT mice generated higher levels of antigen‐specific IgM and IgG, a result not observed in NSG BLT mice. Our studies suggest that NSG‐SGM3 BLT mice show improved human B cell development and permit the generation of antigen‐specific antibody responses to viral infection.