Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Gastroenterol. 2013 Feb;48(2):247-53. doi: 10.1007/s00535-012-0626-8. Epub 2012 Jun 29.
IgG4-related disease (IRD) is characterized by systemic IgG4 antibody responses and by infiltration of IgG4-expressing plasma cells into the affected organs. Although T helper type 2 (Th2) cytokines are implicated in enhanced IgG4 responses, molecular mechanisms accounting for the development of IgG4 antibody responses are poorly defined. Since basophils function as antigen-presenting cells for Th2 responses, we tried to clarify the role of basophils in the development of IgG4 responses in this study.
IgG4 and cytokine responses to various nucleotide-binding oligomerization domain-like receptor and Toll-like receptor (TLR) ligands were examined by using basophils isolated from healthy controls and from patients with IgG4-related disease.
Activation of TLRs in basophils from healthy controls induced IgG4 production by B cells, which effect was associated with enhanced production of B cell activating factor (BAFF) and IL-13. In addition, activation of TLRs in basophils from patients with IRD induced a large amount of IgG4 by B cells from healthy controls. This enhancement of IgG4 production was again associated with BAFF and IL-13.
These data suggest that innate immune responses mediated through TLRs may play a role in the development of IgG4-related disease, in part by production of BAFF from basophils.
IgG4 相关疾病（IRD）的特征是全身性 IgG4 抗体反应，以及 IgG4 表达浆细胞浸润受累器官。尽管辅助性 T 细胞 2（Th2）细胞因子与增强的 IgG4 反应有关，但导致 IgG4 抗体反应发生的分子机制尚未明确。由于嗜碱性粒细胞作为 Th2 反应的抗原呈递细胞发挥作用，因此我们在这项研究中试图阐明嗜碱性粒细胞在 IgG4 反应发展中的作用。
使用从健康对照者和 IgG4 相关疾病患者中分离的嗜碱性粒细胞，检测 IgG4 和细胞因子对各种核苷酸结合寡聚结构域样受体和 Toll 样受体（TLR）配体的反应。
健康对照者的嗜碱性粒细胞 TLR 激活诱导 B 细胞产生 IgG4，其作用与 B 细胞激活因子（BAFF）和白细胞介素-13（IL-13）的产生增强有关。此外，IRD 患者的嗜碱性粒细胞 TLR 激活诱导健康对照者的 B 细胞产生大量 IgG4。这种 IgG4 产生的增强再次与 BAFF 和 IL-13 有关。
这些数据表明，通过 TLR 介导的先天免疫反应可能在 IgG4 相关疾病的发展中发挥作用，部分原因是嗜碱性粒细胞产生 BAFF。
