体内通过Cre诱导的B细胞抗原受体特异性变化证明成熟自身反应性B细胞的快速清除。
Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo.
作者信息
Lam K P, Rajewsky K
机构信息
Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany.
出版信息
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13171-5. doi: 10.1073/pnas.95.22.13171.
Abstract
Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM+ IgD+ B cells in vivo to address the fate of lymphocytes encountering self-antigens at this developmental stage. Expression of an autoreactive BCR on mature B cells leads to their rapid elimination from the periphery, a process that is inhibited by constitutive bcl-2 transgene expression in an antigen dose-dependent manner. Thus, selection of mature B cells into the long-lived peripheral pool does not prevent their deletion upon encounter of self-antigens.
摘要
发育中的自身反应性B细胞在骨髓中编辑其B细胞抗原受体（BCR），当它们无法重新表达无害的BCR时会发生克隆性删除。在此，利用可诱导的Cre-loxP介导的基因倒置在体内改变成熟IgM+IgD+B细胞上BCR的特异性，以探讨在此发育阶段遇到自身抗原的淋巴细胞的命运。成熟B细胞上自身反应性BCR的表达导致它们从外周迅速清除，这一过程受到组成型bcl-2转基因表达的抑制，且呈抗原剂量依赖性。因此，选择成熟B细胞进入长寿外周库并不能阻止它们在遇到自身抗原时被删除。
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