Hypogammaglobulinemia in BLT humanized mice--an animal model of primary antibody deficiency.
Hypogammaglobulinemia in BLT humanized mice--an animal model of primary antibody deficiency.
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DOI：
10.1371/journal.pone.0108663
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Denton PW
中科院分区：
文献类型：
--
作者：
Martinez-Torres F;Nochi T;Wahl A;Garcia JV;Denton PW
原发性抗体缺乏症临床表现为血浆抗体减少或缺失，没有其他可解释免疫球蛋白水平低的已确定疾病。骨髓-肝-胸腺（BLT）人源化小鼠也表现出一抗缺乏或低丙种球蛋白血症。对BLT小鼠B细胞发育和分化的全面表征揭示了与原发性免疫缺陷患者的其他关键相似之处。我们发现，B细胞的个体发育是正常的BLT小鼠的骨髓，但观察到的转换记忆B细胞在外周的情况下。PC-KLH免疫导致在免疫的BLT小鼠中存在转换的记忆B细胞，尽管在组织中未检测到产生PC或KLH特异性IgG的浆细胞。总之，我们已经确定了一抗缺乏患者的体液免疫系统和BLT小鼠的体液免疫系统之间的以下相似之处，这使得该体内模型成为一个强大的和转化的实验平台，用于更好地理解人类中的这种异质性体液免疫缺陷疾病：（i）低丙种球蛋白血症;（ii）骨髓中正常的B细胞个体发育;和（iii）对免疫的抗原特异性IgG应答差。此外，开发克服BLT小鼠中这些体液免疫畸变的策略可能反过来为一些原发性抗体缺乏症患者的发病机制提供见解，这可能导致新的临床干预措施，以改善体液免疫功能。
Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PC- or KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function.
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影响因子：
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