Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing
Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing
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DOI：
10.1016/s1074-7613(00)80586-5
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发表时间：
1998-07-01
期刊：
影响因子：
32.4
通讯作者：
Behrens, TW
中科院分区：
文献类型：
--
作者：
Fang, W;Weintraub, BC;Behrens, TW
在表达膜结合自身抗原（mHEL）的小鼠中，同时转基因表达bcl - x（L）死亡抑制基因和识别鸡卵溶菌酶的免疫球蛋白受体（HEL - Ig）的自身反应性B细胞有效地逃避了发育停滞和缺失。针对相同抗原，不表达bcl - x（L）的转基因HEL - Ig B细胞被清除，而表达bcl - 2的细胞在未成熟B细胞阶段停滞。逃避阴性选择的Bcl - x（L）转基因B细胞在体外和体内实验中均无反应，并显示出一些受体编辑的迹象。这些研究表明，Bcl - x在控制B细胞发育的未成熟阶段的存活方面可能具有独特作用，并证明当自身反应性B细胞逃避中枢性缺失时，耐受性得以维持。
Self-reactive B cells Tg for both a bcl-x(L) death inhibitory gene and an Ig receptor recognizing hen egg lysozyme (HEL-Ig) efficiently escaped developmental arrest and deletion in mice expressing membrane-bound self-antigen (mHEL). In response to the same antigen, Tg HEL-Ig B cells not expressing bcl-x(L) were deleted, while cells expressing bcl-2 were arrested at the immature B stage. Bcl-x(L) Tg B cells escaping negative selection were anergic in both in vitro and in vivo assays and showed some evidence for receptor editing. These studies suggest that Bcl-x may have a distinct role in controlling survival at the immature stage of B cell development and demonstrate that tolerance is preserved when self-reactive B cells escape central deletion.