Deng Chao, Xiang Yufei, Tan Tingting, Ren Zhihui, Cao Chuqing, Huang Gan, Wen Li, Zhou Zhiguang
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.
Section of Endocrinology, Yale School of Medicine, Yale University, New Haven, CT.
Diabetes Care. 2016 Mar;39(3):434-40. doi: 10.2337/dc15-1765. Epub 2015 Dec 30.
B lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes.
Patients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19(+)CD23(-)CD21(+) (marginal zone B [MZB]), CD19(+)CD23(+)CD21(-) (follicular B [FoB]), and CD19(+)CD5(+)CD1d(hi) (interleukin-10-producing regulatory B [B10]) cells by flow cytometry.
Patients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A(1c).
The data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.
B淋巴细胞在自身免疫性糖尿病的免疫发病机制中起重要作用。我们假设B细胞亚群表型的改变与自身免疫性糖尿病相关。
招募1型糖尿病（T1D）患者（n = 81）、成人隐匿性自身免疫性糖尿病（LADA）患者（n = 82）、2型糖尿病（T2D）患者（n = 95）以及糖耐量正常（NGT）的健康对照者（n = 218）。我们通过流式细胞术测定循环B淋巴细胞亚群的百分比，包括CD19(+)CD23(-)CD21(+)（边缘区B细胞[MZB]）、CD19(+)CD23(+)CD21(-)（滤泡B细胞[FoB]）和CD19(+)CD5(+)CD1d(hi)（产生白细胞介素-10的调节性B细胞[B10]）。
与NGT健康对照者和T2D患者相比，T1D或LADA患者的MZB细胞百分比增加，FoB细胞百分比降低。此外，与LADA或T2D患者相比，T1D患者的B10细胞频率最低，而健康对照者的B10细胞频率最高。值得注意的是，MZB细胞频率与空腹C肽（FCP）呈负相关，FoB细胞频率与FCP呈正相关。B10细胞频率与FCP呈正相关，与糖化血红蛋白A1c呈负相关。
数据显示，T1D或LADA患者的B细胞亚群频率发生改变，这与胰岛功能和血糖水平相关。这些发现表明，B淋巴细胞可能参与自身耐受性丧失和β细胞破坏，可作为免疫干预的生物标志物和潜在靶点。
