Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
J Autoimmun. 2015 Jul;61:62-72. doi: 10.1016/j.jaut.2015.05.008. Epub 2015 Jun 11.
Thymic CD4(+) FoxP3(+) regulatory T (Treg) cells are critical for the development of immunological tolerance and immune homeostasis and requires contributions of both thymic dendritic and epithelial cells. Although B cells have been reported to be present within the thymus, there has not hitherto been a definition of their role in immune cell development and, in particular, whether or how they contribute to the Treg cellular thymic compartment. Herein, using both phenotypic and functional approaches, we demonstrate that thymic B cells contribute to the maintenance of thymic Treg cells and, using an in vitro culture system, demonstrate that thymic B cells contribute to the size of the thymic Treg compartment via cell-cell MHC II contact and the involvement of two independent co-stimulatory pathways that include interactions between the CD40/CD80/CD86 co-stimulatory molecules. Our data also suggest that thymic B cells promote the generation of thymic Treg cell precursors (pre-Treg cells), but not the conversion of FoxP3(+) Treg cells from pre-Treg cells. In addition, thymic B cells directly promote the proliferation of thymic Treg cells that is MHC II contact dependent with a minimal if any role for co-stimulatory molecules including CD40/CD80/CD86. Both pathways are independent of TGFβ. In conclusion, we rigorously define the critical role of thymic B cells in the development of thymic Treg cells from non-Treg to precursor stage and in the proliferation of mature thymic Treg cells.
胸腺中的 CD4(+)FoxP3(+)调节性 T(Treg)细胞对于免疫耐受和免疫平衡的发展至关重要，需要胸腺树突状细胞和上皮细胞的共同贡献。尽管已经报道了 B 细胞存在于胸腺中，但它们在免疫细胞发育中的作用尚未得到明确界定，特别是它们是否以及如何有助于 Treg 细胞的胸腺区室。在此，我们使用表型和功能方法证明了胸腺 B 细胞有助于维持胸腺 Treg 细胞，并且使用体外培养系统证明了胸腺 B 细胞通过 MHC II 接触和两个独立的共刺激途径（包括 CD40/CD80/CD86 共刺激分子之间的相互作用）有助于胸腺 Treg 区室的大小。我们的数据还表明，胸腺 B 细胞促进了胸腺 Treg 细胞前体（pre-Treg 细胞）的生成，但不能将 FoxP3(+)Treg 细胞从 pre-Treg 细胞转化而来。此外，胸腺 B 细胞直接促进依赖 MHC II 接触的胸腺 Treg 细胞的增殖，而包括 CD40/CD80/CD86 在内的共刺激分子的作用最小，如果有的话。这两种途径都独立于 TGFβ。总之，我们严格定义了胸腺 B 细胞在 Treg 细胞从非 Treg 到前体阶段的发育以及成熟的胸腺 Treg 细胞的增殖中的关键作用。
