PDF(Pubmed)
Abstract：
Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets. B cell receptor (BCR) somatic hypermutation is a mechanism by which B cells increase affinity for islet autoantigen. High-affinity B and T cell responses are selected in protective immune responses, but immune tolerance mechanisms are known to censor highly autoreactive clones in autoimmunity, including T1D. Thus, different selection rules often apply to autoimmune disease settings (as opposed to protective host immunity), where different autoantigen affinity ceilings are tolerated based on variations in host genetics and environment. This review will explore what is currently known regarding B cell signaling, selection, and interaction with T cells to promote T1D pathogenesis.
摘要：
胰岛自身抗体可预测1型糖尿病（T1D），但在鼠和人T1D中可能是短暂的，并且不被认为是直接致病的。相反，这些自身抗体作为抗原呈递细胞(APC)发出B细胞活性信号,向糖尿病性T细胞呈递胰岛自身抗原以促进T1D发病机制.破坏B细胞APC功能可防止小鼠模型中的T1D，并在临床试验中显示出希望。因此,自身抗原特异性B细胞具有作为复杂的T1D生物标志物和治疗靶标的潜力。B细胞受体（BCR）体细胞超突变是B细胞增加对胰岛自身抗原亲和力的机制。在保护性免疫应答中选择高亲和力B和T细胞应答,但是已知免疫耐受机制会审查自身免疫中的高度自身反应性克隆，包括T1D。因此，不同的选择规则通常适用于自身免疫性疾病设置(与保护性宿主免疫相反)，根据宿主遗传学和环境的变化，可以容忍不同的自身抗原亲和上限。这篇综述将探讨目前已知的关于B细胞信号传导的内容，选择,与T细胞相互作用促进T1D发病机制。
