He Bing, Xu Weifeng, Santini Paul A, Polydorides Alexandros D, Chiu April, Estrella Jeannelyn, Shan Meimei, Chadburn Amy, Villanacci Vincenzo, Plebani Alessandro, Knowles Daniel M, Rescigno Maria, Cerutti Andrea
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Immunity. 2007 Jun;26(6):812-26. doi: 10.1016/j.immuni.2007.04.014.
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 IgA(2) 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.
出生后不久，细菌就会在肠道内定植，此后发挥多种有益功能，包括诱导产生保护性免疫球蛋白A（IgA）抗体。远端肠道含有IgA2，它比IgA1对细菌蛋白酶的抵抗力更强。B细胞从IgM转换为IgA2的机制尚不清楚。我们发现，人类肠道上皮细胞（IECs）通过一种涉及增殖诱导配体（APRIL）的不依赖CD4+T细胞的途径，触发B细胞中的IgA2类别转换，包括来自黏膜滤泡的表达IgA1的B细胞。IECs通过Toll样受体（TLRs）感知细菌后释放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，细菌通过一个需要APRIL的TLR诱导信号程序，将固有层B细胞与IECs联系起来，从而引发IgA2类别转换。因此，黏膜疫苗应激活IECs以诱导更有效的IgA2反应。
