CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles
CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles
复制标题
DOI：
10.2353/ajpath.2007.060817
复制
发表时间：
2007-04-01
影响因子：
6
通讯作者：
Newberry, Rodney D.
中科院分区：
文献类型：
--
作者：
McDonald, Keely G.;McDonough, Jacquelyn S.;Newberry, Rodney D.
孤立的淋巴滤泡（ILF）是有组织的淋巴结构，其促进抗原、抗原呈递细胞和淋巴细胞的有效相互作用，以在肠内产生受控的适应性免疫应答。由于CC趋化因子受体6（CCR 6）缺陷影响粘膜免疫反应的产生，我们评估了CCR 6在ELF发展中的潜在作用。我们观察到CCR 6及其配体CCL 20在ELF中高度表达，并且B淋巴细胞是ILF中最大的CCR 6表达群体。ELF的发展在缺乏CCR 6的情况下被严重抑制。与在对应于B淋巴细胞流入的阶段中HX发育的阻断一致，我们观察到CCR 6缺陷小鼠具有减少的肠B淋巴细胞群体。骨髓重建研究表明，ELF的发展依赖于CCR 6充足的B淋巴细胞，过继转移表明CCR 6（-/-）B淋巴细胞在定位于肠淋巴结构方面效率低下。除了这些发现之外，我们还观察到CCR 6缺陷小鼠派伊尔集合淋巴结B淋巴细胞的比例降低，派伊尔集合淋巴结滤泡圆顶的数量和大小也相应减少。这些观察结果确定了B淋巴细胞在肠淋巴结构定位和HX发育中CCR 6表达的重要作用。
Isolated lymphoid follicles (ILFs) are organized lymphoid structures that facilitate the efficient interaction of antigen, antigen-presenting cells, and lymphocytes to generate controlled adaptive immune responses within the intestine. Because CC chemokine receptor 6 (CCR6) deficiency affects the generation of mucosal immune responses, we evaluated a potential role for CCR6 in the development of ELFs. We observed that CCR6 and its ligand CCL20 are highly expressed within ELFs and that B lymphocytes are the largest CCR6-expressing population within ILFs. ELF development was profoundly arrested in the absence of CCR6. Concordant with a block in HX development at a stage corresponding to the influx of B lymphocytes, we observed that CCR6-deficient mice had a diminished population of intestinal B lymphocytes. Bone marrow reconstitution studies demonstrated that ELF development is dependent on CCR6-sufficient B lymphocytes, and adoptive transfers demonstrated that CCR6(-/-) B lymphocytes were inefficient at localizing to intestinal lymphoid structures. Paralleling these findings, we observed that CCR6-deficient mice had a reduced proportion of Peyer's patch B lymphocytes and an associated reduction in the number and size of Peyer's patch follicular domes. These observations define an essential role for CCR6 expression by B lymphocytes in localizing to intestinal lymphoid structures and in HX development.