Haba S, Nisonoff A
Department of Biology, Brandeis University, Waltham, Massachusetts 02254.
J Exp Med. 1988 Aug 1;168(2):713-24. doi: 10.1084/jem.168.2.713.
We have previously shown that adult A/J mice produce high titers of anti-IgE with isotypic or idiotypic specificities in response to challenge with a conjugate of KLH with syngeneic monoclonal IgE. Thus, B cells that can synthesize anti-IgE are present in the mice. Adult mice are unresponsive to unconjugated IgE in CFA, suggesting that tolerance exists at the level of T cells. The present study shows that neonatal mice produce anti-IgE antibodies in response to unconjugated IgE in CFA, but that this capacity is lost after the age of 2-3 wk. The loss of responsiveness corresponds closely with the appearance of detectable IgE in serum, suggesting that the IgE may induce tolerance. The affinities of anti-IgE antibodies produced by neonatal mice fall in the range of values obtained with KLH-IgE in adult mice. Tolerance to unconjugated IgE in CFA can be induced in neonatal mice by administration of IgE in saline. In addition, the tolerant state can be induced by adoptive transfer of spleen cells from adult mice. The time-dependent acquisition of tolerance provides a useful model for studying mechanisms of tolerance and autoimmunity.
我们之前已经表明,成年A/J小鼠在受到钥孔戚血蓝蛋白(KLH)与同基因单克隆IgE的偶联物攻击后,会产生高滴度的具有同种型或独特型特异性的抗IgE。因此,这些小鼠体内存在能够合成抗IgE的B细胞。成年小鼠对弗氏完全佐剂(CFA)中未偶联的IgE无反应,这表明在T细胞水平存在耐受性。本研究表明,新生小鼠在受到CFA中未偶联的IgE攻击后会产生抗IgE抗体,但这种能力在2 - 3周龄后会丧失。反应性的丧失与血清中可检测到的IgE的出现密切相关,这表明IgE可能诱导耐受性。新生小鼠产生的抗IgE抗体的亲和力与成年小鼠中用KLH - IgE获得的值范围相同。通过在盐水中给予IgE,可在新生小鼠中诱导对CFA中未偶联IgE的耐受性。此外,通过成年小鼠脾细胞的过继转移也可诱导耐受状态。耐受性的时间依赖性获得为研究耐受和自身免疫机制提供了一个有用的模型。