ELIMINATION FROM PERIPHERAL LYMPHOID-TISSUES OF SELF-REACTIVE LYMPHOCYTES-B RECOGNIZING MEMBRANE-BOUND ANTIGENS
ELIMINATION FROM PERIPHERAL LYMPHOID-TISSUES OF SELF-REACTIVE LYMPHOCYTES-B RECOGNIZING MEMBRANE-BOUND ANTIGENS
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DOI：
10.1038/353765a0
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发表时间：
1991-10-24
期刊：
影响因子：
64.8
通讯作者：
GOODNOW, CC
中科院分区：
文献类型：
--
作者：
HARTLEY, SB;CROSBIE, J;GOODNOW, CC
长期存在的假设1,2认为，对自身抗原的耐受性是由自身反应性淋巴细胞的消除3-8或功能失活（能量；参考9-11）介导的，这一假设现在已被接受，但对启动其中一个过程而不是另一个过程的因素知之甚少。在b细胞谱系中，耐受性自身反应细胞在表达溶菌酶和抗溶菌酶免疫球蛋白基因9的转基因小鼠的外周淋巴器官中持续存在，但在表达抗主要组织相容性复合体免疫球蛋白基因8的类似转基因小鼠中被消除。通过修改溶菌酶转基因的结构和抗溶菌酶免疫球蛋白基因的同型，我们在这里证明了能量或缺失的诱导不是由于抗体亲和力或同型的差异，而是由于对单体或寡聚可溶性抗原与高多价膜结合抗原的识别。我们的研究结果表明，受体交联的程度可以对淋巴细胞的发育产生质的不同的信号后果。
THE long-standing hypothesis 1,2 that tolerance to self antigens is mediated by either elimination 3-8 or functional inactivation (anergy; refs 9-11) of self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral lymphoid organs of transgenic mice expressing lysozyme and anti-lysozyme immunoglobulin genes 9, but are eliminated in similar transgenic mice expressing anti-major histocompatibility complex immunoglobulin genes 8. By modifying the structure of the lysozyme transgene and the isotype of the anti-lysozyme immunoglobulin genes, we demonstrate here that induction of anergy or deletion is not due to differences in antibody affinity or isotype, but to recognition of monomeric or oligomeric soluble antigen versus highly multivalent membrane-bound antigen. Our findings indicate that the degree of receptor crosslinking can have qualitatively distinct signalling consequences for lymphocyte development.