Intestinal bacteria trigger T cell-independent immunoglobulin A2 class switching by inducing epithelial-cell secretion of the cytokine APRIL
Intestinal bacteria trigger T cell-independent immunoglobulin A2 class switching by inducing epithelial-cell secretion of the cytokine APRIL
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DOI：
10.1016/j.immuni.2007.04.014
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发表时间：
2007-06-01
期刊：
影响因子：
32.4
通讯作者：
Cerutti, Andrea
中科院分区：
文献类型：
--
作者：
He, Bing;Xu, Weifeng;Cerutti, Andrea
细菌在出生后不久就在肠道定植，此后发挥几种有益的功能，包括诱导保护性免疫球蛋白A（伊加）抗体。远端肠道含有伊加（2），其对细菌蛋白酶的抵抗力比伊加（1）更强。B细胞从IgM转变为伊加的机制尚不清楚。我们发现，人肠上皮细胞（IEC）通过涉及增殖诱导配体（APRIL）的CD4（+）T细胞非依赖性途径触发了B细胞（包括来自粘膜滤泡的表达伊加（1）的B细胞）中伊加（2）的类别转换。IEC通过Toll样受体（TLR）感应细菌后释放APRIL，并通过胸腺基质淋巴细胞生成素激活树突状细胞进一步增加APRIL的产生。我们的数据表明，细菌通过连接固有层B细胞与IEC通过TLR诱导的信号程序需要APRIL引起IgA 2类转换。因此，粘膜疫苗应该激活IEC以诱导更有效的伊加（2）应答。
Bacteria colonize the intestine shortly after birth and thereafter exert several beneficial functions, including induction of protective immunoglobulin A (IgA) antibodies. The distal intestine contains IgA(2), which is more resistant to bacterial proteases than is IgA(1). The mechanism by which B cells switch from IgM to IgA(2) remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA(2) class switching in B cells, including IgA(1)-expressing B cells arriving from mucosal follicles, through a CD4(+) T cell-independent pathway involving a proliferation-inducing ligand (APRIL). IECs released APRIL after sensing bacteria through Toll-like receptors (TLRs) and further increased APRIL production by activating dendritic cells via thymic stromal lymphopoietin. Our data indicate that bacteria elicit IgA2 class switching by linking lamina propria B cells with IECs through a TLR-inducible signaling program requiring APRIL. Thus, mucosal vaccines should activate IECs to induce more effective IgA(2) responses.