Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system.
Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system.
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DOI：
10.1007/978-3-540-75647-7_6
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发表时间：
2008
影响因子：
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通讯作者：
R. Ito;M. Shiina;Y. Saito;Y. Tokuda;Y. Kametani;S. Habu
中科院分区：
文献类型：
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作者：
R. Ito;M. Shiina;Y. Saito;Y. Tokuda;Y. Kametani;S. Habu
被动抗体给药作为一种新的治疗方法显示出强大的潜力。在临床应用中，具有抗原特异性的人源性抗体更有用，而不会使个体处于危险之中。如果在动物中建立了人免疫系统，则可以从动物模型中获得针对给定抗原的人源抗体的产生。事实上，过去的报道揭示了人类T和B细胞是从免疫缺陷小鼠的造血祖细胞发育而来的。然而，在用人免疫细胞重建的免疫缺陷小鼠中充分诱导抗原特异性抗体，特别是IgG的报道很少。在这一章中，我们讨论了一个主要的缺点，诱导抗原特异性IgG抗体在人类免疫细胞在小鼠环境中开发的基础上，我们的数据。我们证明了人T细胞发育受到鼠MHC的限制，因此T细胞可能无法与人B细胞实现同源相互作用。小鼠体内发育的人B细胞主要是CD 5 +B1细胞，优先产生IgM。同时，脾上移植人LN使NOG小鼠产生抗原特异性IgG抗体。这些结果表明，如果在人T和B-2细胞之间发生由MHC II类上的某种抗原介导的有效同源相互作用，则人B细胞可以在鼠环境中产生针对给定抗原的IgG抗体。
Passive antibody administration shows strong potential as a new therapeutic method. In clinical applications, human-derived antibodies with antigen specificity are more useful without putting individuals at risk. Production of human-derived antibodies against given antigens can be obtained from animal models if the human immune system is established in the animals. In fact, past reports revealed that human T and B cells develop from hematopoietic progenitor cells in immunodeficient mice. However, there have been few reports on sufficient induction of antigen-specific antibodies, particularly IgG, in immunodeficient mice reconstituted with human immune cells. In this chapter, we discuss a major shortcoming of induction of antigen-specific IgG antibodies in human immune cells developed in the murine environment based on our data. We demonstrated that human T cell development is restricted by the murine MHC and consequently T cells may not achieve cognate interaction with human B cells. Human B cells developed in the mouse are mainly CD5+B1 cells that preferentially produce IgM. At the same time, human LN transplantation on the spleen enabled NOG mice to produce antigen-specific IgG antibody. These results suggest that if efficient cognate interaction mediated by a certain antigen on MHC class II between human T and B-2 cells occurs, human B cells can produce IgG antibody against a given antigen in the murine environment.