离体
生发中心
免疫系统
类有机物
细胞生物学
生物
体内
免疫学
B细胞
抗体
生物技术
作者
Alberto Purwada,Manish K. Jaiswal,Haelee Ahn,Toshio Nojima,Daisuke Kitamura,Akhilesh K. Gaharwar,Leandro Cerchietti,Ankur Singh
出处
期刊:Biomaterials
[Elsevier]
日期:2015-09-01
卷期号:63: 24-34
被引量:108
标识
DOI:10.1016/j.biomaterials.2015.06.002
摘要
Ex vivo engineered three-dimensional organotypic cultures have enabled the real-time study and control of biological functioning of mammalian tissues. Organs of broad interest where its architectural, cellular, and molecular complexity has prevented progress in ex vivo engineering are the secondary immune organs. Ex vivo immune organs can enable mechanistic understanding of the immune system and more importantly, accelerate the translation of immunotherapies as well as a deeper understanding of the mechanisms that lead to their malignant transformation into a variety of B and T cell malignancies. However, till date, no modular ex vivo immune organ has been developed with an ability to control the rate of immune reaction through tunable design parameter. Here we describe a B cell follicle organoid made of nanocomposite biomaterials, which recapitulates the anatomical microenvironment of a lymphoid tissue that provides the basis to induce an accelerated germinal center (GC) reaction by continuously providing extracellular matrix (ECM) and cell-cell signals to naïve B cells. Compared to existing co-cultures, immune organoids provide a control over primary B cell proliferation with ∼100-fold higher and rapid differentiation to the GC phenotype with robust antibody class switching.
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