Department of Immunology, Landspítali-University Hospital, Reykjavík, Iceland.
Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Front Immunol. 2018 Apr 27;9:909. doi: 10.3389/fimmu.2018.00909. eCollection 2018.
Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells. Here, we analyze the phenotype and function of T and B cells in individuals with IgAD following IgA-inducing CpG-TLR9 stimulations. The IgAD individuals had significantly lower numbers of transitional B cells (CD19CD24CD38) and class-switched memory B cells (CD20CD27IgD) . However, proportions of T cell populations as well as induced T effector cells and T regulatory cells were comparable to healthy controls. After CpG stimulation, the transitional B cell defect was further enhanced, especially within its B regulatory subset expressing IL-10. Finally, CpG stimulation failed to induce IgA production in IgAD individuals. Collectively, our results demonstrate a defect of the TLR9 responses in IgAD that leads to B cell dysregulation and decreased IgA production.
选择性 IgA 缺乏症（IgAD）是西方世界最常见的原发性抗体缺乏症，受影响个体的自身免疫、特应性疾病和感染负担增加。已经表明，IgAD B 细胞可以通过模仿生发中心的反应被诱导产生 IgA。然而，IgA 是粘膜部位最常见的抗体，在这些部位，抗原非依赖性反应很重要。最近，人们对 TLR9 在幼稚和成熟 B 细胞分化为分泌 IgA 的浆细胞中的作用产生了浓厚的兴趣。在这里，我们分析了 IgA 诱导的 CpG-TLR9 刺激后 IgAD 个体中的 T 和 B 细胞的表型和功能。IgAD 个体的过渡性 B 细胞（CD19^+CD24^+CD38^+）和类别转换记忆 B 细胞（CD20^+CD27^+IgD^-）数量明显减少。然而，T 细胞群体的比例以及诱导的 T 效应细胞和 T 调节细胞与健康对照组相当。CpG 刺激后，过渡性 B 细胞缺陷进一步增强，特别是在表达 IL-10 的 B 调节亚群中。最后，CpG 刺激未能诱导 IgAD 个体产生 IgA。总的来说，我们的结果表明 IgAD 中 TLR9 反应存在缺陷，导致 B 细胞失调和 IgA 产生减少。
