Endotypes in T1D: B lymphocytes and early onset.
Endotypes in T1D: B lymphocytes and early onset.
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DOI：
10.1097/med.0000000000000547
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Gottlieb PA
中科院分区：
文献类型：
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作者：
Smith MJ;Cambier JC;Gottlieb PA
虽然1型糖尿病（T1D）的特征在于自身反应性T细胞对胰腺β细胞的破坏，但越来越明显的是，B细胞也在疾病发展中起主要作用，可能充当抗原呈递细胞。在这里，我们回顾了胰岛抗原反应性B细胞的生物学及其参与自身免疫性糖尿病。相对于晚发型，在早期发展为T1D的个体在胰岛中显示胰岛素反应性B细胞的积累增加。这种B细胞特征也与疾病的快速进展和对B细胞耗竭疗法的反应性相关。高亲和力胰岛素反应性B细胞无反应性的丧失也提示B细胞参与疾病。重要的是，在携带某些T1D风险等位基因的患者健康一级亲属中观察到无反应性的丧失，这表明在疾病发展的早期起作用。最近的研究表明，胰岛反应性B细胞可能在年轻患者的T1D发展的非常早期起致病作用，并建议靶向这些细胞的治疗的效用。
While Type 1 diabetes (T1D) is characterized by destruction of the pancreatic beta cells by self-reactive T cells, it has become increasingly evident that B cells also play a major role in disease development, likely functioning as antigen presenting cells. Here we review the biology of islet antigen-reactive B cells and their participation in autoimmune diabetes. Relative to late onset, individuals who develop T1D at an early age display increased accumulation of insulin-reactive B cells in islets. This B cell signature is also associated with rapid progression of disease and responsiveness to B cell depletion therapy. Also suggestive of B cell participation in disease is loss of anergy in high affinity insulin-reactive B cells. Importantly, loss of anergy is seen in patient’s healthy first degree relatives carrying certain T1D risk alleles, suggesting a role early in disease development. Recent studies indicate that islet-reactive B cells may play a pathogenic role very early in T1D development in young patients, and suggest utility of therapies that target these cells.