Maddur Mohan S, Sharma Meenu, Hegde Pushpa, Stephen-Victor Emmanuel, Pulendran Bali, Kaveri Srini V, Bayry Jagadeesh
1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris F-75006, France [2] Centre de Recherche des Cordeliers, Equipe 16- Immunopathology and Therapeutic Immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris F-75006, France [3] Université Paris Descartes, UMR S 1138, Paris F-75006, France [4] Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris F-75006, France [2] Université de Technologie de Compiègne, Compiègne F-60205, France.
Nat Commun. 2014 Jun 9;5:4092. doi: 10.1038/ncomms5092.
Dendritic cells (DCs) play a critical role in immune homeostasis by regulating the functions of various immune cells, including T and B cells. Notably, DCs also undergo education on reciprocal signalling by these immune cells and environmental factors. Various reports demonstrated that B cells have profound regulatory functions, although only few reports have explored the regulation of human DCs by B cells. Here we demonstrate that activated but not resting B cells induce maturation of DCs with distinct features to polarize Th2 cells that secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is contact dependent and implicates signalling of B-cell activation molecules CD69, B-cell-activating factor receptor, and transmembrane activator and calcium-modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2 cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our results suggest that B cells have the ability to control their own effector functions by enhancing the ability of human DCs to mediate Th2 differentiation.
树突状细胞(DCs)通过调节包括T细胞和B细胞在内的各种免疫细胞的功能,在免疫稳态中发挥关键作用。值得注意的是,DCs也会受到这些免疫细胞和环境因子的相互信号传导的影响。各种报告表明B细胞具有深远的调节功能,尽管只有少数报告探讨了B细胞对人DCs的调节作用。在这里,我们证明活化而非静止的B细胞可诱导具有不同特征的DCs成熟,从而使分泌白细胞介素(IL)-5、IL-4和IL-13的Th2细胞极化。B细胞诱导的DCs成熟是接触依赖性的,涉及B细胞活化分子CD69、B细胞活化因子受体以及跨膜激活剂和钙调节亲环素配体相互作用分子的信号传导。从机制上讲,B细胞成熟的DCs诱导Th2细胞分化依赖于OX-40配体。总的来说,我们的结果表明B细胞具有通过增强人DCs介导Th2分化的能力来控制自身效应功能的能力。