Pabst Oliver, Ohl Lars, Wendland Meike, Wurbel Marc-André, Kremmer Elisabeth, Malissen Bernard, Förster Reinhold
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
J Exp Med. 2004 Feb 2;199(3):411-6. doi: 10.1084/jem.20030996. Epub 2004 Jan 26.
Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.
肠道相关淋巴组织中的体液免疫的特征是固有层中分泌抗体的浆细胞（PCs）产生免疫球蛋白A（IgA）。趋化因子CCL25由肠上皮细胞表达，并且在体外能够诱导IgA+浆细胞的趋化作用。利用新产生的针对小鼠CCR9的单克隆抗体，我们发现IgA+浆细胞在肠系膜淋巴结（MLN）和派尔集合淋巴结（PPs）中高水平表达CCR9，但一旦它们定位于小肠中，CCR9表达就下调。在CCR9缺陷小鼠中，小肠固有层中IgA+浆细胞的数量大幅减少。在过继转移实验中，与野生型对照相比，CCR9缺陷的IgA+浆细胞向小肠的迁移减少。此外，尽管PPs和MLN的结构和细胞类型组成未受影响且对IgA浆细胞的产生仍有功能，但CCR9突变体对口服抗原不能产生正常的IgA应答。这些发现提供了深刻的体内证据，证明CCL25/CCR9引导浆细胞进入小肠。
