Xiao Bao-Guo, Duan Rui-Sheng, Link Hans, Huang Yu-Min
NEUROTEC Department, Karolinska Institute, Alfred Nobels Alle 10, SE-141 83, Stockholm, Sweden.
Cell Immunol. 2003 May;223(1):63-9. doi: 10.1016/s0008-8749(03)00118-7.
Dendritic cells (DC) are usually regarded as antigen-presenting cells involved in T cell activation, but DC also directly and indirectly affect B cell activation, antibody synthesis, and isotype switch. In the present study, bone marrow (BM)-derived DC from healthy rats were pulsed in vitro with acetylcholine receptor (AChR) and injected subcutaneously into healthy Lewis rats. No clinical signs of the first phase of experimental autoimmune myasthenia gravis (EAMG) were observed during 3 weeks of observation. Upon immunization with AChR and complete Freund's adjuvant, the rats that had received AChR-pulsed DC did not develop clinical EAMG. This tolerance of rats injected with AChR-pulsed DC was associated with reduced expression of B cell-activating factor (BAFF) and by reduced numbers of B cells among splenic mononuclear cells (MNC) compared to rats injected with medium or unpulsed DC. Anti-AChR IgG antibody-secreting cells were decreased, while the ratio of IgG1:IgG2b isotypes was enhanced in rats treated with AChR-pulsed DC compared to control EAMG rats. These results demonstrate that AChR-pulsed DC induce peripheral tolerance to EAMG by possibly inhibiting the expression of BAFF and production of anti-AChR antibodies, providing a possible potential for immunotherapy of antibody-mediated autoimmune diseases.
树突状细胞（DC）通常被视为参与T细胞活化的抗原呈递细胞，但DC也直接或间接影响B细胞活化、抗体合成和亚型转换。在本研究中，将来自健康大鼠的骨髓（BM）源性DC在体外与乙酰胆碱受体（AChR）一起脉冲处理，然后皮下注射到健康的Lewis大鼠体内。在3周的观察期内，未观察到实验性自身免疫性重症肌无力（EAMG）第一阶段的临床症状。在用AChR和完全弗氏佐剂免疫后，接受AChR脉冲DC的大鼠未出现临床EAMG。与注射培养基或未脉冲DC的大鼠相比，注射AChR脉冲DC的大鼠的这种耐受性与B细胞活化因子（BAFF）表达降低以及脾单核细胞（MNC）中B细胞数量减少有关。与对照EAMG大鼠相比，用AChR脉冲DC处理的大鼠中分泌抗AChR IgG抗体的细胞减少，而IgG1:IgG2b亚型的比例增加。这些结果表明，AChR脉冲DC可能通过抑制BAFF的表达和抗AChR抗体的产生来诱导对EAMG的外周耐受，为抗体介导的自身免疫性疾病的免疫治疗提供了一种可能的潜力。
