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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Activated B cells modified by electroporation of multiple mRNAs encoding immune stimulatory molecules are comparable to mature dendritic cells in inducing in vitro antigen-specific T-cell responses.
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Activated B cells modified by electroporation of multiple mRNAs encoding immune stimulatory molecules are comparable to mature dendritic cells in inducing in vitro antigen-specific T-cell responses.

机译：通过电穿孔编码免疫刺激分子的多个mRNA修饰的活化B细胞在诱导体外抗原特异性T细胞反应方面与成熟树突状细胞相当。

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Ex-vivo-activated B cells are an alternative source of antigen-presenting cells (APCs) and a potential replacement for dendritic cells (DCs) in immunotherapy. However, the ability of ex-vivo-activated B cells to function as potent APCs has been a concern, especially when compared to DCs. Our study investigated whether modification of activated B cells with immune stimulatory molecules could enhance the ability of activated B cells to stimulate T cells. We show that murine splenic B cells, activated with a combination of Toll-like receptor agonist and agonistic anti-CD40, stimulated antigen-specific CD8+ T cells more efficiently than cells activated with Toll-like receptor agonist or anti-CD40 alone, probably by down-regulation of the immune regulatory cytokine interleukin-10 (IL-10). However, the activated B cells were still poor T-cell stimulators compared to mature DCs. Therefore, we modified the activated B cells by simultaneous electroporation of multiple messenger RNAs encoding costimulatory molecules (OX40L and 4-1BBL), cytokines (IL-12p35 and IL-12p40) and antigen. We found that de novo expression or overexpression of OX40L, 4-1BBL and IL-12p70 on activated B cells synergistically enhanced proliferation as well as IL-2 and interferon-gamma production by CD8+ T cells. Furthermore, the RNA-modified activated B cells induced antigen-specific cytotoxic T lymphocyte responses as efficiently as mature DCs in vitro. Unexpectedly, modified activated B cells were inferior to mature DCs at in vivo induction of CD8+ T-cell responses. In summary, activated B cells modified to express immune stimulatory molecules are a potent alternative to DCs in immunotherapy.
机译：活体外激活的B细胞是抗原呈递细胞（APC）的替代来源，并且在免疫疗法中可能替代树突状细胞（DC）。然而，离体激活的B细胞作为有效APC的能力一直受到关注，特别是与DC相比。我们的研究调查了用免疫刺激分子修饰活化的B细胞是否可以增强活化的B细胞刺激T细胞的能力。我们显示，与Toll样受体激动剂或抗CD40单独激活的细胞相比，用Toll样受体激动剂和激动性抗CD40组合激活的小鼠脾B细胞更有效地刺激了抗原特异性CD8 + T细胞。下调免疫调节细胞因子白介素10（IL-10）。但是，与成熟的DC相比，活化的B细胞仍然是不良的T细胞刺激剂。因此，我们通过同时电穿孔编码信使分子（OX40L和4-1BBL），细胞因子（IL-12p35和IL-12p40）和抗原的多个信使RNA修饰了活化的B细胞。我们发现，在活化的B细胞上从头表达或过表达OX40L，4-1BBL和IL-12p70协同增强CD8 + T细胞的增殖以及IL-2和干扰素-γ的产生。此外，在体外，RNA修饰的活化B细胞与成熟DC一样有效地诱导抗原特异性细胞毒性T淋巴细胞反应。出乎意料的是，在体内诱导CD8 + T细胞反应时，修饰的活化B细胞不如成熟DC。总之，在免疫疗法中，修饰为表达免疫刺激分子的活化B细胞是DC的有效替代品。

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