Receptor editing and genetic variability in human autoreactive B cells.
Receptor editing and genetic variability in human autoreactive B cells.
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DOI：
10.1084/jem.20151039
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发表时间：
2016-01-11
期刊：
影响因子：
--
通讯作者：
Pelanda R
中科院分区：
文献类型：
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作者：
Lang J;Ota T;Kelly M;Strauch P;Freed BM;Torres RM;Nemazee D;Pelanda R
Lang等人在人源化的小鼠模型中表明，人类B细胞通过接收器编辑和克隆缺失的结合进行中心耐受性。
在小鼠中，B细胞（例如受体编辑，克隆缺失和厌恶）的机制已在小鼠中建立。种植了人类免疫系统。通过遵循自反应性人κ+ B细胞的命运，我们表明，人类B细胞的耐受性是在自我遇到的第一个位置发生的，通过受体编辑的组合，骨髓的结合，可在可用的自我供应范围内供应范围对于研究特定可能是有用的人类B细胞耐受性的机制，并揭示人类种群中这一过程程度的差异。
Lang et al. show in a humanized mouse model that human B cells undergo central tolerance via a combination of receptor editing and clonal deletion. The mechanisms by which B cells undergo tolerance, such as receptor editing, clonal deletion, and anergy, have been established in mice. However, corroborating these mechanisms in humans remains challenging. To study how autoreactive human B cells undergo tolerance, we developed a novel humanized mouse model. Mice expressing an anti–human Igκ membrane protein to serve as a ubiquitous neo self-antigen (Ag) were transplanted with a human immune system. By following the fate of self-reactive human κ+ B cells relative to nonautoreactive λ+ cells, we show that tolerance of human B cells occurs at the first site of self-Ag encounter, the bone marrow, via a combination of receptor editing and clonal deletion. Moreover, the amount of available self-Ag and the genetics of the cord blood donor dictate the levels of central tolerance and autoreactive B cells in the periphery. Thus, this model can be useful for studying specific mechanisms of human B cell tolerance and to reveal differences in the extent of this process among human populations.