Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1-and CD106 (VCAM-1)-dependent mechanism
Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1-and CD106 (VCAM-1)-dependent mechanism
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DOI：
10.1172/jci11092
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发表时间：
2001-02-01
影响因子：
15.9
通讯作者：
Kipps, TJ
中科院分区：
文献类型：
--
作者：
Burger, JA;Zvaifler, NJ;Kipps, TJ
B 细胞积聚和异位生发中心的形成是类风湿性关节炎 (RA) 患者患病关节的特征性变化。早期研究表明，B 淋巴细胞与 RA 滑膜特有的特殊滑膜“护士样”细胞之间的相互作用可能是滑膜中 B 细胞的归巢和持续存活的原因。然而，在这项研究中，我们发现 B 细胞自发地迁移到普通成纤维样滑膜细胞 (FLS) 下方，然后存活时间延长。从骨关节炎患者关节中分离出的 FLS 也支持这种称为 B 细胞假伸入的活动。我们发现FLS组成性表达趋化因子基质细胞衍生因子1（SDF-1），并且百日咳毒素或SDF-1受体抗体（CXCR4）可以抑制B细胞假伸入。然而，SDF-1 的表达是不够的，因为真皮成纤维细胞也表达这种趋化因子，但无法支持 B 细胞假伸入，除非事先用 IL-4 刺激表达 CD106 (VCAM-1)，α (4)β (1) 整联蛋白的配体，极晚期抗原 4（VLA-4 或 CD49d）。此外，mAb 对 CD49d 和 CD106 或合成的 CS1 纤连蛋白肽具有特异性，可以抑制 B 细胞假伸入。我们得出的结论是，普通 FLS 可以通过依赖于成纤维细胞 SDF-1 和 CD106 表达的机制支持 B 细胞假伸入。
B-cell accumulation and formation of ectopic germinal centers are characteristic changes in the diseased joints of patients with rheumatoid arthritis (RA). Earlier studies suggested that interactions between B lymphocytes and specialized synovial "nurse-Like" cells peculiar to die RA synovium may be responsible for the homing and sustained survival of B cells in the synovium. However, in this study we found that B cells spontaneously migrate beneath ordinary fibroblast-like synoviocytes (FLSs) and then experience prolonged survival. FLSs isolated from joints of patients with osteoarthritis also supported this activity termed B-cell pseudoemperipolesis. We found that FLSs constitutively expressed the chemokine stromal cell-derived factor-1 (SDF-1), and that pertussis toxin or antibodies to the SDF-1 receptor (CXCR4) could inhibit B-cell pseudoemperipolesis. However, expression of SDF-1 is not sufficient, as dermal fibroblasts also expressed this chemokine but were unable to support B-cell pseudoemperipolesis unless previously stimulated with IL-4 to express CD106 (VCAM-1), a ligand for the alpha (4)beta (1) integrin, very-late-antigen-4 (VLA-4 or CD49d). Furthermore, mAb's specific for CD49d and CD106, or the synthetic CS1 fibronectin peptide, could inhibit B-cell pseudoemperipolesis. We conclude that ordinary FLSs can support B-cell pseudoemperipolesis via a mechanism dependent upon fibroblast expression of SDF-1 and CD106.