IgA的产生需要B细胞与派尔集合淋巴结中的上皮下树突状细胞相互作用。

IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches.

作者信息

Reboldi Andrea, Arnon Tal I, Rodda Lauren B, Atakilit Amha, Sheppard Dean, Cyster Jason G

机构信息

Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Lung Biology Center, Department of Medicine, University of California San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.

出版信息

Science. 2016 May 13;352(6287):aaf4822. doi: 10.1126/science.aaf4822.

Immunoglobulin A (IgA) induction primarily occurs in intestinal Peyer's patches (PPs). However, the cellular interactions necessary for IgA class switching are poorly defined. Here we show that in mice, activated B cells use the chemokine receptor CCR6 to access the subepithelial dome (SED) of PPs. There, B cells undergo prolonged interactions with SED dendritic cells (DCs). PP IgA class switching requires innate lymphoid cells, which promote lymphotoxin-β receptor (LTβR)-dependent maintenance of DCs. PP DCs augment IgA production by integrin αvβ8-mediated activation of transforming growth factor-β (TGFβ). In mice where B cells cannot access the SED, IgA responses against oral antigen and gut commensals are impaired. These studies establish the PP SED as a niche supporting DC-B cell interactions needed for TGFβ activation and induction of mucosal IgA responses.

免疫球蛋白A（IgA）的诱导主要发生在肠道派尔集合淋巴结（PP）中。然而，IgA类别转换所必需的细胞间相互作用仍不清楚。在这里，我们表明在小鼠中，活化的B细胞利用趋化因子受体CCR6进入PP的上皮下圆顶区（SED）。在那里，B细胞与SED树突状细胞（DC）进行长时间的相互作用。PP中的IgA类别转换需要固有淋巴细胞，它们促进DC的淋巴毒素-β受体（LTβR）依赖性维持。PP DC通过整合素αvβ8介导的转化生长因子-β（TGFβ）激活来增强IgA的产生。在B细胞无法进入SED的小鼠中，针对口服抗原和肠道共生菌的IgA反应受损。这些研究将PP SED确立为一个支持TGFβ激活和诱导粘膜IgA反应所需的DC-B细胞相互作用的生态位。