Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Diabetes Research Unit Cymru, Grove Building, Swansea University, Swansea SA2 8PP, UK.
J Immunol Methods. 2019 Aug;471:61-65. doi: 10.1016/j.jim.2019.05.007. Epub 2019 May 29.
Type 1 diabetes mellitus (T1D) is an autoimmune disorder where T lymphocytes damage the islet beta cells but B lymphocytes also play an important role. Although changes in peripheral B cell phenotype have been observed, little is known about the B cells that secrete the autoantibodies. We developed a sensitive B cell enzyme-linked immunospot assay (ELISpot assay) to detect individual B cell antibody responses to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2). We found that even healthy donors have B cells that secrete antibodies in response to GAD and IA-2 in the ELISpot. There was increased B cell reactivity to autoantigens in the peripheral blood of individuals with newly-diagnosed, but not long-standing, type 1 diabetes. However, no correlation with serum autoantibody levels was found, indicating that additional factors such as antigen affinity or exposure to antigens in vivo are required for antibody secretion, and that even healthy donors have potentially autoreactive B cells.
1 型糖尿病（T1D）是一种自身免疫性疾病，其中 T 淋巴细胞会损伤胰岛β细胞，但 B 淋巴细胞也起着重要作用。尽管已经观察到外周 B 细胞表型的变化，但对于分泌自身抗体的 B 细胞知之甚少。我们开发了一种灵敏的 B 细胞酶联免疫斑点检测（ELISpot 检测），以检测针对谷氨酸脱羧酶（GAD）和胰岛抗原-2（IA-2）的个体 B 细胞抗体反应。我们发现，即使是健康的供体，在 ELISpot 中也会有分泌针对 GAD 和 IA-2 的抗体的 B 细胞。在新诊断但尚未长期存在的 1 型糖尿病患者的外周血中，B 细胞对自身抗原的反应性增加。然而，与血清自身抗体水平没有相关性，这表明需要其他因素，如抗原亲和力或体内抗原暴露，才能进行抗体分泌，并且即使是健康的供体也可能具有潜在的自身反应性 B 细胞。
