de Vries M J, Hijmans W
Immunology. 1967 Feb;12(2):179-96.
An extensive histological study was carried out of NZB, NZW and (NZB × NZW)F, (BWF), mice of all ages between birth and 18 months. The thymuses of these mice were compared to those of three normal mouse strains. The study of the NZW mice showed that these mice, although they only occasionally have weakly positive Coombs' tests, may develop a renal disease probably of an autoimmune nature, similar to that of the NZB and the BWF mice. Mice of all the three NZ strains developed lesions of the skin, liver, intestines, lymphatic tissues and kidneys much resembling those occurring in human systemic lupus erythematosus (SLE), neonatally thymectomized mice and, with the exception of the renal changes, the lesions of graft host disease. The comparative study of the thymus in autoimmune and normal strains, revealed that important changes of the large medullary epithelial cells, involved in the formation of Hassall's corpuscles, occur very early in the three autoimmune strains. In the NZB mice the large epithelial cells are severely decreased in number in the first weeks following birth. The depletion of epithelial cells could be ascribed to a secondary degeneration of these cells soon after birth. In contrast with the NZB mice, an extensive hyperplasia of the large epithelial cells and Hassall's corpuscles was observed in the NZW and BWF mice, and was already apparent in the newborn animal. Many of the epithelial aggregates seemed to have been invaded by lymphoid cells. Both epithelial cells and the lymphoid cells engaged in this process showed a variety of degenerative changes. As in the NZB, a depletion of epithelial cells occurred in a later phase, at the age of 8 months in the BWF and at 1 year in the NZW. In the majority of young mice of the normal strains invasion of islands of epithelial cells by lymphoid cells may also be observed, although this process is far less extensive than in the autoimmune strains and does not result in either epithelial hyperplasia or depletion of epithelial cells. The described phenomenon of invasion of epithelial structures in the thymus by subsequently disintegrating lymphoid cells seems to support Burnet's concept, that so-called `forbidden clones' of lymphoid cells are eliminated in the thymus.
对出生至18个月龄的NZB、NZW和(NZB×NZW)F1(BWF)小鼠进行了全面的组织学研究。将这些小鼠的胸腺与三种正常小鼠品系的胸腺进行了比较。对NZW小鼠的研究表明,这些小鼠虽然仅偶尔有弱阳性的库姆斯试验,但可能会发生一种可能具有自身免疫性质的肾脏疾病,类似于NZB和BWF小鼠的疾病。所有这三种新西兰品系的小鼠都出现了皮肤、肝脏、肠道、淋巴组织和肾脏的病变,与人类系统性红斑狼疮(SLE)、新生期胸腺切除的小鼠以及除肾脏变化外的移植物抗宿主病的病变非常相似。对自身免疫品系和正常品系胸腺的比较研究表明,参与哈氏小体形成的大型髓质上皮细胞的重要变化在三种自身免疫品系中很早就出现了。在NZB小鼠中,出生后的头几周大型上皮细胞数量严重减少。上皮细胞的耗竭可归因于出生后不久这些细胞的继发性变性。与NZB小鼠相反,在NZW和BWF小鼠中观察到大型上皮细胞和哈氏小体广泛增生,并且在新生动物中就已明显。许多上皮聚集体似乎已被淋巴细胞侵入。参与这一过程的上皮细胞和淋巴细胞都表现出各种退行性变化。与NZB一样,上皮细胞耗竭发生在后期,BWF小鼠在8个月龄时,NZW小鼠在1岁时。在大多数正常品系的幼鼠中,也可观察到淋巴细胞侵入上皮细胞岛,尽管这一过程远比自身免疫品系中的要少,且不会导致上皮增生或上皮细胞耗竭。所述的淋巴细胞随后解体侵入胸腺上皮结构的现象似乎支持了伯内特的概念,即所谓的淋巴细胞“禁忌克隆”在胸腺中被清除。