INTRINSIC B-CELL HYPORESPONSIVENESS ACCOUNTS FOR SELF-TOLERANCE IN LYSOZYME ANTILYSOZYME DOUBLE-TRANSGENIC MICE
INTRINSIC B-CELL HYPORESPONSIVENESS ACCOUNTS FOR SELF-TOLERANCE IN LYSOZYME ANTILYSOZYME DOUBLE-TRANSGENIC MICE
复制标题
DOI：
10.1073/pnas.87.15.5687
复制
发表时间：
1990-08-01
影响因子：
11.1
通讯作者：
GOODNOW, CC
中科院分区：
文献类型：
--
作者：
ADAMS, E;BASTEN, A;GOODNOW, CC
在双转基因小鼠中，表达编码鸡蛋溶菌酶的基因构建体以及重排的抗溶菌酶抗体基因，大量的抗溶菌酶B细胞存在于外周淋巴组织中，但具有深刻的耐受性。探索了这种非缺失自我耐受形式的细胞基础。从双转基因小鼠的耐受性抗溶菌酶B细胞被发现比非转基因对照产生更少的抗体在T细胞依赖性抗原特异性反应，在体内过继转移，在体外悬滴培养，以及在响应刺激与非特异性丝裂原脂多糖。耐受性B细胞的反应性降低不是由于反应性B细胞前体本身的数量减少，也不是由于在滴定、耗竭或混合实验中检测到抑制细胞。因此，该模型中的非缺失耐受性似乎是由自身反应性B细胞本身的内在功能变化引起的。
In double-transgenic mice expressing a gene construct encoding hen egg lysozyme as well as rearranged anti-lysozyme antibody genes, large numbers of anti-lysozyme B cells are present in peripheral lymphoid tissues but are profoundly tolerant. The cellular basis for this form of non-deletional self-tolerance was explored. The tolerant anti-lysozyme B cells from double-transgenic mice were found to produce much less antibody than nontransgenic controls in T-cell-dependent antigen-specific responses, in adoptive transfer in vivo, and in hanging-drop cultures in vitro, as well as in response to stimulation with the nonspecific mitogen lipolysaccharide. The diminished responsiveness of the tolerant B cells was not due to a reduction in the number of responding B-cell precursors per se nor were suppressor cells detected in titration, depletion, or mixing experiments. Nondeletion tolerance in this model, therefore, appears to result from an intrinsic functional change in the self-reactive B cells themselves.