Engineering early memory B-cell-like phenotype in hydrogel-based immune organoids.

Engineering early memory B-cell-like phenotype in hydrogel-based immune organoids.
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DOI:
10.1002/jbm.a.37388
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发表时间:
2022-08
期刊:
Journal of biomedical materials research. Part A
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记忆B细胞起源于次级淋巴器官的B细胞滤泡,在次级淋巴器官的B细胞滤泡中,幼稚的B细胞在亚解剖微环境中成熟,即生发中心。对记忆B细胞免疫学及其调节的理解主要基于涉及小鼠模型的复杂实验。到目前为止,关于记忆B细胞能否成功地在体外工程,特别是使用支持B细胞生长和分化的生物材料平台的证据有限。在这里,我们报告了最近报道的马来酰亚胺功能化的聚乙二醇水凝胶作为免疫器官的特征,以促进早期记忆B细胞表型和生发中心样B细胞的发展。我们证明,使用白介素9(IL9)、IL21和细菌抗原提呈作为外膜结合片段,可以在体外免疫器官中将幼稚的原代小鼠B细胞转化为早期记忆表型。这些发现描述了免疫器官中早期记忆B细胞样表型的诱导,并强调了合成器官作为未来发展抗原特异性真实记忆B细胞的平台的潜力,用于免疫系统的研究和治疗性抗体的产生。
Memory B cells originate in response to antigenic stimulation in B-cell follicles of secondary lymphoid organs where naive B cells undergo maturation within a sub-anatomical microenvironment, the germinal centers. The understanding of memory B-cell immunology and its regulation is based primarily on sophisticated experiments that involve mouse models. To date, limited evidence exists on whether memory B cells can be successfully engineered ex vivo, specifically using biomaterials-based platforms that support the growth and differentiation of B cells. Here, we report the characterization of a recently reported maleimide-functionalized poly(ethylene glycol) (PEG) hydrogels as immune organoids towards the development of early memory B-cell phenotype and germinal center-like B cells. We demonstrate that the use of interleukin 9 (IL9), IL21, and bacterial antigen presentation as outer membrane-bound fragments drives the conversion of naive, primary murine B cells to early memory phenotype in ex vivo immune organoids. These findings describe the induction of early memory B-cell-like phenotype in immune organoids and highlight the potential of synthetic organoids as a platform for the future development of antigen-specific bona fide memory B cells for the study of the immune system and generation of therapeutic antibodies.
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期刊: IMMUNITY
影响因子: 32.4
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先天淋巴样细胞会整合基质和免疫信号,从而增强脾脏边缘区B细胞的抗体产生。
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影响因子: 30.5
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