Sun Jianbo, Wang Jiguang, Pefanis Evangelos, Chao Jaime, Rothschild Gerson, Tachibana Isao, Chen Jun Kui, Ivanov Ivaylo I, Rabadan Raul, Takeda Yoshito, Basu Uttiya
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Systems Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cell Rep. 2015 Nov 10;13(6):1110-1117. doi: 10.1016/j.celrep.2015.09.070. Epub 2015 Oct 29.
Regulatory B cells (Breg) have immune suppressive functions in various autoimmune/inflammation models and diseases and are found to be enriched in diverse B cell subsets. The lack of a unique marker or set of markers efficiently identifying Breg cells impedes detailed investigation into their origin, development, and immunological roles. Here, we perform transcriptome analysis of IL-10-expressing B cells to identify key regulators for Breg biogenesis and function and identify CD9, a tetraspanin-family transmembrane protein, as a key surface marker for most mouse IL-10(+) B cells and their progenitors. CD9 plays a role in the suppressive function of IL-10(+) B cells in ex vivo T cell proliferation assays through a mechanism that is dependent upon B/T cell interactions. CD9(+) B cells also demonstrate inhibition of Th1-mediated contact hypersensitivity in an in vivo model system. Taken together, our findings implicate CD9 in the immunosuppressive activity of regulatory B cells.
调节性B细胞(Breg)在各种自身免疫/炎症模型和疾病中具有免疫抑制功能,并且发现其在多种B细胞亚群中富集。缺乏有效识别Breg细胞的独特标志物或标志物组合阻碍了对其起源、发育和免疫作用的详细研究。在此,我们对表达白细胞介素10(IL-10)的B细胞进行转录组分析,以鉴定Breg细胞生成和功能的关键调节因子,并确定CD9(一种四跨膜蛋白家族的跨膜蛋白)为大多数小鼠IL-10(+)B细胞及其祖细胞的关键表面标志物。在体外T细胞增殖试验中,CD9通过一种依赖于B/T细胞相互作用的机制,在IL-10(+)B细胞的抑制功能中发挥作用。在体内模型系统中,CD9(+)B细胞也表现出对Th1介导的接触性超敏反应的抑制作用。综上所述,我们的研究结果表明CD9参与调节性B细胞的免疫抑制活性。