Knight J, Laing P, Knight A, Adams D, Ling N
J Clin Endocrinol Metab. 1986 Feb;62(2):342-7. doi: 10.1210/jcem-62-2-342.
Burnet's "forbidden clone" theory would predict that in patients with Graves' disease the pathogenic thyroid-stimulating autoantibody (TSab)-secreting clones arise by somatic mutation. Because each lymphocyte and its progeny are permanently committed to producing antibodies of a single light chain type, a clone arising by somatic mutation occurring in a single cell would be expected to produce autoantibodies of exclusively kappa or exclusively lambda type in an individual patient. Using affinity chromatographic techniques and monoclonal antibodies, we investigated the light chain type of TSab in 11 patients with Graves' disease. In all patients tested, TSab activity was confined to a single light chain type, confirming the recent work of Zakarija who used affinity chromatography with polyclonal antisera, but contrasting with earlier studies which used immuno-precipitation methods. Furthermore, the light chain type was lambda in 10 of the 11 patients. These observations provide support for the forbidden clone theory. In addition, the marked preponderance of patients producing TSab of the lambda-light chain type indicates that TSab are more likely to arise from the lambda repertoire of clones than from the kappa repertoire and suggests that immunoglobulin light chain V genes may be genetic determinants for susceptibility to Graves' disease.
伯内特的“禁忌克隆”理论预测，在格雷夫斯病患者中，产生致病性促甲状腺素自身抗体（TSab）的克隆是通过体细胞突变产生的。由于每个淋巴细胞及其后代永久性地致力于产生单一轻链类型的抗体，因此预计在单个细胞中通过体细胞突变产生的克隆会在个体患者中产生仅为κ型或仅为λ型的自身抗体。我们使用亲和色谱技术和单克隆抗体，研究了11例格雷夫斯病患者中TSab的轻链类型。在所有测试患者中，TSab活性局限于单一轻链类型，这证实了扎卡里亚最近使用多克隆抗血清进行亲和色谱的研究结果，但与早期使用免疫沉淀方法的研究结果形成对比。此外，11例患者中有10例的轻链类型为λ型。这些观察结果为禁忌克隆理论提供了支持。此外，产生λ轻链型TSab的患者明显占优势，这表明TSab更有可能来自λ克隆库而非κ克隆库，并提示免疫球蛋白轻链V基因可能是格雷夫斯病易感性的遗传决定因素。
