Department of Immunology, Jagiellonian University Medical College, 31-121 Krakow, Poland.
Section of Rheumatology, Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, CT 06520, USA.
Int J Mol Sci. 2018 Sep 7;19(9):2656. doi: 10.3390/ijms19092656.
Antibody light chains (LCs), formerly considered a waste product of immunoglobulin synthesis, are currently recognized as important players in the activation of the immune response. However, very little is known about the possible immune regulatory functions of LCs. Recently, we reported that hapten-specific LCs coat miRNA-150-carrying exosomes produced by CD8+ suppressor T cells downregulating the contact hypersensitivity (CHS) reaction in an antigen-specific manner, in mice tolerized by intravenous administration of a high dose of hapten-coupled syngeneic erythrocytes. Thus, the current studies aimed at investigating the role of hapten-specific LCs in antigen-specific, exosome-mediated suppression of CHS effector cells. Suppressor T cell-derived exosomes from tolerized B-cell-deficient µMT, NKT-cell-deficient Jα18, and immunoglobulin-deficient JH mice were nonsuppressive, unless supplemented with LCs of specificity strictly respective to the hapten used for sensitization and CHS elicitation in mice. Thus, these observations demonstrate that B1-cell-derived LCs, coating exosomes in vivo and in vitro, actually ensure the specificity of CHS suppression. Our research findings substantially expand current understanding of the newly discovered, suppressor T cell-dependent tolerance mechanism by uncovering the function of antigen-specific LCs in exosome-mediated, cell⁻cell communication. This express great translational potential in designing nanocarriers for specific targeting of desired cells.
抗体轻链 (LC) 曾被认为是免疫球蛋白合成的废物产物，但目前被认为是免疫反应激活的重要参与者。然而，人们对 LC 可能的免疫调节功能知之甚少。最近，我们报道了半抗原特异性 LC 可覆盖 CD8+抑制性 T 细胞产生的 miRNA-150 携带的外泌体，以抗原特异性方式下调接触超敏反应 (CHS) 反应，在小鼠中通过静脉给予高剂量偶联半抗原的同源红细胞进行耐受。因此，目前的研究旨在研究半抗原特异性 LC 在抗原特异性、外泌体介导的 CHS 效应细胞抑制中的作用。来自耐受 B 细胞缺陷 µMT、NKT 细胞缺陷 Jα18 和免疫球蛋白缺陷 JH 小鼠的抑制性 T 细胞衍生的外泌体是无抑制作用的，除非补充与用于小鼠致敏和 CHS 引发的半抗原特异性严格相应的 LC。因此，这些观察结果表明，B1 细胞衍生的 LC 在体内和体外覆盖外泌体，实际上确保了 CHS 抑制的特异性。我们的研究结果大大扩展了对新发现的、依赖抑制性 T 细胞的耐受机制的现有理解，揭示了抗原特异性 LC 在体外和体外外泌体介导的细胞间通讯中的功能。这在设计用于特定靶向所需细胞的纳米载体方面具有巨大的转化潜力。
