Haynes G A, Maini R N, Malcolm A D
Department of Biochemistry, Charing Cross and Westminster Medical School, London.
Ann Rheum Dis. 1990 Jun;49 Suppl 1:460-8.
Antibodies to exogenous antigen and to self antigen--that is, autoantibodies, are both encoded by the combining of V, D, and J genetic elements in the heavy chain, and V and J in the light chain immunoglobulins. The mechanism which generates autoantibodies does not seem to differ from that which generates the immune response to foreign antigen, and analysis of DNA from normal and autoimmune strains of mice appears similar with no appreciable defects in the immunoglobulin germline genes. Although there is restricted use of particular gene families in murine antibodies to exogenous antigen, the preferential use of particular V genes in murine autoantibodies remains controversial. Until recently, because of the obvious limitations on human experimentation, there was little information about the genetics of the human autoimmune response. Recent developments in molecular cloning techniques, however, some of which are discussed here, have shown that the germline arrangement of the human immunoglobulin variable genes differs from that found in the mouse. Furthermore, there is increasing evidence that human autoantibodies make restricted use of the V gene repertoire, and this indicates that the human autoimmune response is less polymorphic than the murine autoimmune response.
针对外源性抗原和自身抗原的抗体——即自身抗体，均由重链中V、D和J基因元件以及轻链免疫球蛋白中V和J基因元件的组合进行编码。产生自身抗体的机制似乎与产生针对外来抗原的免疫反应的机制并无不同，对正常小鼠和自身免疫小鼠品系的DNA分析显示二者相似，免疫球蛋白种系基因没有明显缺陷。尽管在小鼠针对外源性抗原的抗体中特定基因家族的使用受到限制，但在小鼠自身抗体中特定V基因的优先使用仍存在争议。直到最近，由于人体实验存在明显限制，关于人类自身免疫反应遗传学的信息很少。然而，分子克隆技术的最新进展，本文将讨论其中一些进展，表明人类免疫球蛋白可变基因的种系排列与小鼠不同。此外，越来越多的证据表明人类自身抗体对V基因库的使用有限，这表明人类自身免疫反应的多态性低于小鼠自身免疫反应。
