Exeter Centre for Excellence in Diabetes (EXCEED), University of Exeter Medical School, Exeter, United Kingdom.
Front Endocrinol (Lausanne). 2021 Feb 25;12:617437. doi: 10.3389/fendo.2021.617437. eCollection 2021.
Significant progress has been made in understanding the phenotypes of circulating immune cell sub-populations in human type 1 diabetes but much less is known about the equivalent populations that infiltrate the islets to cause beta-cell loss. In particular, considerable uncertainties remain about the phenotype and role of B-lymphocytes in the pancreas. This gap in understanding reflects both the difficulty in accessing the gland to study islet inflammation during disease progression and the fact that the number and proportion of islet-associated B-lymphocytes varies significantly according to the disease endotype. In very young children (especially those <7 years at onset) pancreatic islets are infiltrated by both CD8+ T- and CD20+ B-lymphocytes in roughly equal proportions but it is widely held that the CD8+ T-lymphocytes are responsible for driving beta-cell toxicity. By contrast, the role played by B-lymphocytes remains enigmatic. This is compounded by the fact that, in older children and teenagers (those ≥13 years at diagnosis) the proportion of B-lymphocytes found in association with inflamed islets is much reduced by comparison with those who are younger at diagnosis (reflecting two endotypes of disease) whereas CD8+ T-lymphocytes form the predominant population in both groups. In the present paper, we review the current state of understanding and develop a proposal to stimulate further discussion of the roles played by islet-associated B-lymphocytes in human type 1 diabetes. We cite evidence indicating that sites of direct contact can be found between CD8+ and CD20+-lymphocytes in and around inflamed islets and propose that such interactions may be important in determining the efficiency of beta cell killing.
在理解人类 1 型糖尿病中循环免疫细胞亚群的表型方面已经取得了重大进展，但对于浸润胰岛导致β细胞损失的等效细胞群知之甚少。特别是，关于在胰腺中 B 淋巴细胞的表型和作用仍存在相当大的不确定性。这种理解上的差距反映了两个方面的困难：一是在疾病进展过程中难以进入腺体来研究胰岛炎症；二是胰岛相关 B 淋巴细胞的数量和比例根据疾病的终末表型而有很大差异。在非常年幼的儿童（尤其是发病时年龄<7 岁的儿童）中，胰岛被 CD8+ T 细胞和 CD20+B 细胞大致均等浸润，但人们普遍认为 CD8+ T 细胞是导致β细胞毒性的原因。相比之下，B 淋巴细胞的作用仍然是个谜。事实情况更加复杂，在年龄较大的儿童和青少年（发病时年龄≥13 岁）中，与炎症胰岛相关的 B 淋巴细胞的比例与发病年龄较小的儿童相比大大降低（反映了两种疾病终末表型），而 CD8+ T 细胞在这两个群体中都构成了主要群体。在本文中，我们回顾了目前的理解状态，并提出了一个建议，以激发进一步讨论胰岛相关 B 淋巴细胞在人类 1 型糖尿病中的作用。我们引用了表明在炎症胰岛内外可以发现 CD8+和 CD20+淋巴细胞之间直接接触部位的证据，并提出这种相互作用可能对确定β细胞杀伤的效率很重要。
