Wallenberg Laboratory for Cardiovascular Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Clin Exp Immunol. 2013 Oct;174(1):129-38. doi: 10.1111/cei.12148.
B-1 lymphocytes produce natural immunoglobulin (Ig)M, among which a large proportion is directed against apoptotic cells and altered self-antigens, such as modified low-density lipoprotein (LDL). Thereby, natural IgM maintains homeostasis in the body and is also protective against atherosclerosis. Diabetic patients have an increased risk of developing certain infections as well as atherosclerosis compared with healthy subjects, but the underlying reason is not known. The aim of this study was to investigate whether diabetes and insulin resistance affects B-1 lymphocytes and their production of natural IgM. We found that diabetic db/db mice had lower levels of peritoneal B-1a cells in the steady state-condition compared to controls. Also, activation of B-1 cells with the Toll-like receptor (TLR)-4 agonist Kdo2-Lipid A or immunization against Streptococcus pneumoniae led to a blunted IgM response in the diabetic db/db mice. In-vitro experiments with isolated B-1 cells showed that high concentrations of glucose, but not insulin or leptin, caused a reduced secretion of total IgM and copper-oxidized (CuOx)-LDL- and malondialdehyde (MDA)-LDL-specific IgM from B-1 cells in addition to a decreased differentiation into antibody-producing cells, proliferation arrest and increased apoptosis. These results suggest that metabolic regulation of B-1 cells is of importance for the understanding of the role of this cell type in life-style-related conditions.
B-1 淋巴细胞产生天然免疫球蛋白（Ig）M，其中很大一部分针对凋亡细胞和自身改变的抗原，如修饰的低密度脂蛋白（LDL）。因此，天然 IgM 维持着体内的内稳态，并且对动脉粥样硬化也有保护作用。与健康受试者相比，糖尿病患者发生某些感染和动脉粥样硬化的风险增加，但背后的原因尚不清楚。本研究旨在探讨糖尿病和胰岛素抵抗是否会影响 B-1 淋巴细胞及其天然 IgM 的产生。我们发现，与对照组相比，稳定状态下糖尿病 db/db 小鼠的腹腔 B-1a 细胞水平较低。此外，用 Toll 样受体（TLR）-4 激动剂 Kdo2-Lipid A 或肺炎链球菌免疫激活 B-1 细胞会导致糖尿病 db/db 小鼠的 IgM 反应减弱。与分离的 B-1 细胞的体外实验表明，高浓度的葡萄糖，而不是胰岛素或瘦素，会导致 B-1 细胞分泌总 IgM 和铜氧化（CuOx）-LDL-和丙二醛（MDA）-LDL 特异性 IgM 减少，同时分化为产生抗体的细胞减少、增殖停滞和凋亡增加。这些结果表明，B-1 细胞的代谢调节对于理解这种细胞类型在与生活方式相关的条件中的作用非常重要。
