Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, USA.
Cell Mol Immunol. 2013 Jul;10(4):311-6. doi: 10.1038/cmi.2013.17. Epub 2013 Apr 29.
Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag(-/-) mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag(-/-) mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.
磷酸胆碱（PC）是许多微生物表面发现的免疫显性表位，包括肺炎链球菌（SPn），被认为在 SPn 的发病机制中起着至关重要的作用。已经表明，表达针对 PC 的 M167Hκ24L 免疫球蛋白受体的 B 细胞在 X 连锁免疫缺陷和 Rag（-/-）小鼠中具有自身反应性，因为它们经历了克隆删除。我们现在已经表明，表达 M603Hκ8L PC 特异性受体的 B 细胞也在 Rag（-/-）小鼠中删除，而表达 T15Hκ22L 转基因的 B 细胞则不会删除。然而，由于 T15Hκ22L B 细胞不能与正常 B 细胞竞争，因此在正常杂合转基因小鼠中丢失。这些数据表明，M167Hκ24L 和 M603Hκ8L PC 特异性 B 细胞正在识别表达在膜上的自身抗原，导致它们下调其受体并进行克隆性删除，而 T15Hκ22L B 细胞则通过 PC-抗原的可溶性形式被耐受，导致它们被困在脾脏中。因此，自身反应性 PC 特异性 B 细胞中观察到的耐受类型取决于表达的受体的独特型。
