Department of Molecular Medicine and Pathology, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
Postgrad Med J. 2012 Apr;88(1038):226-33. doi: 10.1136/postgradmedj-2011-130364. Epub 2012 Feb 10.
More than 60 years ago, Burnet first proposed the 'forbidden clone' hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral self-antigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate B-T cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.
60 多年前，Burnet 首次提出了“禁止克隆”假说，该假说假设自身免疫性疾病是由于淋巴细胞的自身反应性克隆持续存在而产生的，这些自身反应性克隆本应通过免疫耐受而被删除。这些自身反应性克隆可以通过外周自身抗原识别来引起免疫介导的靶器官损伤。最近的证据跨越了许多医学专业的界限，支持了这一假设，暗示 B 细胞前体是罪魁祸首。B 细胞耗竭疗法在类风湿关节炎、抗中性粒细胞胞质抗体（ANCA）相关性血管炎、多发性肌炎、狼疮以及多发性硬化症和特发性血小板减少性紫癜等自身免疫性疾病中的成功应用支持了这一假设。在许多自身免疫性疾病中已经描述了 B 细胞和浆细胞的克隆性，以及自身抗体的存在，这些自身抗体可能在临床疾病出现前数年就出现了，这支持了 B 细胞系内自身反应性的观点。在靶器官内 T 细胞的激活可以通过同源 B-T 细胞相互作用来预测，而由此产生的组织炎症和破坏可能会产生由自身免疫性 B 细胞的原始特异性决定的多种临床表现。
