Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris, France.
Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, France.
Immunol Rev. 2019 Jan;287(1):50-61. doi: 10.1111/imr.12720.
The human adaptive immune system recognizes almost all the pathogens that we encounter and all the tumor antigens that may arise during our lifetime. Primary immunodeficiencies affecting lymphocyte development or function therefore lead to severe infections and tumor susceptibility. Furthermore, the fact that autoimmunity is a frequent feature of primary immunodeficiencies reveals a third function of the adaptive immune system: its self-regulation. Indeed, the generation of a broad repertoire of antigen receptors (via a unique strategy of random somatic rearrangements of gene segments in T cell and B cell receptor loci) inevitably creates receptors with specificity for self-antigens and thus leads to the presence of autoreactive lymphocytes. There are many different mechanisms for controlling the emergence or action of autoreactive lymphocytes, including clonal deletion in the primary lymphoid organs, receptor editing, anergy, suppression of effector lymphocytes by regulatory lymphocytes, and programmed cell death. Here, we review the genetic defects affecting lymphocyte apoptosis and that are associated with lymphoproliferation and autoimmunity, together with the role of somatic mutations and their potential involvement in more common autoimmune diseases.
人类适应性免疫系统几乎可以识别我们所遇到的所有病原体和一生中可能出现的所有肿瘤抗原。因此，影响淋巴细胞发育或功能的原发性免疫缺陷会导致严重感染和肿瘤易感性。此外，自身免疫是原发性免疫缺陷的常见特征，这揭示了适应性免疫系统的第三个功能：自我调节。事实上，通过在 T 细胞和 B 细胞受体基因座中进行基因片段的随机体细胞重排的独特策略，产生广泛的抗原受体库不可避免地会产生特异性识别自身抗原的受体，从而导致自身反应性淋巴细胞的存在。有许多不同的机制可以控制自身反应性淋巴细胞的出现或作用，包括初级淋巴器官中的克隆删除、受体编辑、失能、调节性淋巴细胞对效应淋巴细胞的抑制以及程序性细胞死亡。在这里，我们综述了影响淋巴细胞凋亡并与淋巴增殖和自身免疫相关的遗传缺陷，以及体细胞突变的作用及其在更常见的自身免疫性疾病中的潜在参与。
