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首页> 外文期刊>BMC Immunology >B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses
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B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

机译:表达B7h的树突状细胞和血浆B细胞在T细胞依赖性抗体反应中介导ICOS共刺激的不同结果

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Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both na?ve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.
机译:背景ICOS-B7h共刺激受体-配体对是生发中心的形成,同型转换抗体的产生以及对T细胞依赖性抗原的抗体亲和力成熟所必需的。然而,尚未定义在B细胞和树突状细胞中调节的B7h表达在T细胞依赖性抗体应答中的潜在独特作用。结果我们产生了谱系受限的B7h表达的转基因小鼠,以评估B7h表达对B细胞和树突状细胞在调节T细胞依赖性抗体应答中的细胞类型特异性作用。我们的结果表明,与天然和生发中心B细胞相比,体外激活后,B细胞的内源性B7h表达降低,而抗体分泌的血浆B细胞在体内也降低。 B-B7hTg小鼠中激活的B细胞和血浆B细胞上B7h表达水平的提高导致免疫后产生的分泌抗体的浆细胞数量增加,并且相应的抗原特异性高亲和力血清IgG抗体浓度增加。所有同种型,而不会影响响应的生发中心B细胞的数量。相比之下,DC-B7hTg小鼠中树突状细胞介导的ICOS共刺激有助于生发中心的形成,并选择性增加IgG2a的产生,而不会影响抗体反应的整体强度。结论使用具有谱系限制的B7h表达的转基因小鼠,我们揭示了树突状细胞和B细胞介导的ICOS共刺激在调节T细胞依赖性抗体应答中的独特作用。

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