B cell/antibody tolerance to our own antigens
B cell/antibody tolerance to our own antigens
复制标题
DOI：
10.2741/1456
复制
发表时间：
2004-09-01
影响因子：
3.1
通讯作者：
Sinclair, NRS
中科院分区：
文献类型：
--
作者：
Sinclair, NRS
淋巴系统通常对感染性病原体产生破坏性反应，同时避免对自身产生同样的破坏性反应。形成了相当数量的针对自身抗原的抗体，但通常保持在低于破坏性阈值的水平，只是在对传染性非自身的保护性反应中暂时上升到破坏性水平。许多机制调节自身抗体和抗自身B细胞的水平，包括缺失、能量、对抗原的无知、受体编辑、共抑制、资源竞争以维持B细胞反应，以及排斥或遏制外来入侵者后损伤反应的凋亡结局。虽然感染事件可能会促进对自身抗原的免疫反应，但感染事件往往也会加强调节机制。当调节机制不能正常发挥作用时，可能会发生对自身抗原的异常损伤反应。虽然单一调节机制的缺陷可能导致自身免疫，但这种可能性通常只发生在允许的遗传背景下；这表明，其他调节机制的弱点可能是导致对自身抗原产生破坏性反应的必要条件。免疫系统及其调节机制并不简单，正如人们所期望的那样，这是一个平衡过程，它在受到挑战时也有能力大幅扩张，在威胁过去时迅速收缩。这些避免破坏抗自身B细胞的过程比标准的两个信号模型所设想的要复杂得多。通过B细胞抗原受体的简单信号可能促进B细胞存活和接受性，而其他信号（共刺激或共抑制）促进B细胞刺激或非刺激/失活。
The lymphoid system normally mounts damaging responses to infectious pathogens while avoiding equally damaging responses to self. A notable number of antibodies to self antigens are formed but normally remain at levels below the damaging threshold, only temporarily rising to damaging levels during protective responses against infectious nonself. Many mechanisms regulate the level of autoantibodies and anti-self B cells including deletion, anergy, ignorance for antigen, receptor editing, coinhibition, competition for resources to sustain B cell responses, and apoptotic denouement of damaging responses following the ejection or containment of foreign invaders. While infectious events may encourage immune responses to self antigens, infectious events tend also to strengthen regulatory mechanisms. When regulatory mechanisms do not function properly, abnormal damaging responses to self antigens may occur. While defects in a single regulatory mechanism may result in autoimmunity, this eventuality usually happens only on permissive genetic backgrounds; this indicates that weakness in other regulatory mechanisms may be necessary to result in the emergence of damaging responses to self antigens. The immune system and its regulatory mechanisms are not simple, as one would expect of a homoeostatic process that also has the ability to expand enormously when challenged and to contract rapidly when threats pass. These processes that avoid damaging anti-self B cells are much more complicated than that envisaged in standard two signal models. Simple signals through the B cell antigen-receptor probably encourage B cell survival and receptivity, while other signals (costimulatory or coinhibitory) promote B cell stimulation or non-stimulation/inactivation.