Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses
Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses
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DOI：
10.1038/icb.2016.68
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Koerner, Heinrich
中科院分区：
文献类型：
--
作者：
Reimer, Dorothea;Lee, Adrian Y. S.;Koerner, Heinrich
CC-趋化因子受体6（CCR 6）可以在初始和活化的B细胞上检测到。与直觉相反，它的缺乏加速了生发中心（GC）的出现，并增加了低亲和力抗体的产生。CCR 6在体液应答过程中功能的详细机制仍然难以捉摸，但以前我们在抗原激发后早期在体内鉴定了一个独特的CCR 6（高）B细胞群。在这项研究中，我们将这一群体具体定义为早期活化的前GC B细胞。与此一致，我们表明，CCR 6在体外激活后的蛋白质或mRNA水平上在数小时内迅速上调。此外，只有活化的B细胞特异性地向CCL 20迁移，CCL 20是CCR 6的特异性配体。CCR 6的缺乏增加了GC的暗区/亮区比率，并导致在混合骨髓嵌合体中以B细胞固有方式产生的抗原特异性IgG 1和IgG 2a抗体减少。相比之下，抗原特异性IgM反应正常。因此，CCR 6负调节活化的抗原特异性前GC B细胞进入GC反应。
The CC-chemokine receptor 6 (CCR6) can be detected on naive and activated B cells. Counterintuitively, its absence accelerates the appearance of germinal centres (GCs) and increases the production of low-affinity antibodies. The detailed mechanism of CCR6 function during the humoral response has remained elusive, but previously we identified a distinct CCR6(high) B-cell population in vivo early after antigenic challenge. In this study, we defined this population specifically as early, activated pre-GC B cells. In accordance, we show that CCR6 is upregulated rapidly within hours on the protein or mRNA level after activation in vitro. In addition, only activated B cells migrated specifically towards CCL20, the specific ligand for CCR6. Lack of CCR6 increased the dark zone/light zone ratio of GC and led to decreased antigen-specific IgG1 and IgG2a antibody generation in a B-cell intrinsic manner in mixed bone marrow chimeras. In contrast, antigen-specific IgM responses were normal. Hence, CCR6 negatively regulates entry of activated, antigen-specific pre-GC B cells into the GC reaction.