Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells.
Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells.
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DOI：
10.1177/1753425916651985
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发表时间：
2016-08
期刊：
影响因子：
3.2
通讯作者：
Levy O
中科院分区：
文献类型：
--
作者：
Pettengill MA;van Haren SD;Li N;Dowling DJ;Bergelson I;Jans J;Ferwerda G;Levy O
新生儿的先天免疫与成人不同，这可能会增加感染的易感性并限制疫苗反应。 B 细胞在防止感染方面发挥着关键作用，并通过 TLR 检测 PAMP，当与 CD40 共同激活时，可以驱动 B 细胞增殖和抗体产生。我们表征了新生儿和成人循环 B 细胞中 TLR 的表达，并评估了 TLR 和 CD40 介导的幼稚 B 细胞类别转换重组 (CSR) 和细胞因子的产生。新生儿和成人 B 细胞之间大多数 TLR 的基因表达水平相似，但新生儿幼稚 B 细胞比成人幼稚 B 细胞表达更多的 TLR9。新生儿幼稚 B 细胞表现出 TLR2 和 TLR7 受损，但 TLR9 介导的细胞因子产生增强。接受 CSR 产生 IgG 的新生儿幼稚 B 细胞明显减少，IL-21 刺激也会导致这种损害。此外，通过 CD40 和 TLR 的共刺激诱导成体 B 细胞产生更多的细胞因子。因此，虽然新生儿幼稚 B 细胞表现出成人水平的 TLR 和 CD40 表达，但对这些受体刺激的反应是不同的。 TLR9 相对较高的表达和 CD40 介导的 Ig 分泌受损有助于人类新生儿独特的先天性和适应性免疫，并可能为生命早期免疫的新方法提供信息。
Neonatal innate immunity is distinct from that of adults, which may contribute to increased susceptibility to infection and limit vaccine responses. B cells play critical roles in protection from infection and detect PAMPs via TLRs, that, when co-activated with CD40, can drive B cell proliferation and antibody production. We characterized the expression of TLRs in circulating B cells from newborns and adults, and evaluated TLR- and CD40-mediated naïve B cell class-switch recombination (CSR) and cytokine production. Gene expression levels of most TLRs was similar between newborn and adult B cells, except newborn naïve B cells expressed more TLR9 than adult naïve B cells. Neonatal naïve B cells demonstrated impaired TLR2- and TLR7- but enhanced TLR9-mediated cytokine production. Significantly fewer newborn naïve B cells underwent CSR to produce IgG, an impairment also noted with IL-21 stimulation. Additionally, co-stimulation via CD40 and TLRs induced greater cytokine production in adult B cells. Thus, while newborn naïve B cells demonstrate adult-level expression of TLRs and CD40, the responses to stimulation of these receptors are distinct. Relatively high expression of TLR9 and impaired CD40-mediated Ig secretion contributes to distinct innate and adaptive immunity of human newborns and may inform novel approaches to early life immunization.