Antigen-driven clonal proliferation of a cells within the target tissue of an autoimmune disease - The salivary glands of patients with Sjogren's syndrome
Antigen-driven clonal proliferation of a cells within the target tissue of an autoimmune disease - The salivary glands of patients with Sjogren's syndrome
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DOI：
10.1172/jci3234
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发表时间：
1998-09-01
影响因子：
15.9
通讯作者：
Berek, C
中科院分区：
文献类型：
--
作者：
Stott, DI;Hiepe, F;Berek, C
在干燥综合征患者的唾液腺中观察到类似于生发中心的结构，但尚不清楚这些细胞簇的微环境是否足以诱导生发中心反应。因此，我们克隆和测序重排的IG V基因表达的B细胞分离的唇唾液腺活检切片从两个干燥综合征患者。重排的V基因从B细胞内的一个细胞簇是多克隆的，大多数有很少的体细胞突变。来自另一个患者的两个相邻簇各自包含一个表达高度突变的V基因的显性B细胞克隆。在这两个簇中都没有发现重排的V基因，这表明细胞不能迁移到周围组织中并产生新的簇;框架和互补决定区中的置换与沉默突变的比率表明高亲和力突变体的抗原选择。这些结果表明抗原驱动的，在干燥综合征患者的唾液腺内发生了生发中心型B细胞反应。鉴于最近的证明，在类风湿性滑膜和存在类似的结构，在其他自身免疫性疾病的靶组织内的germinal中心的反应，我们建议，germinal中心型反应可以诱导在各种自身免疫性疾病的非淋巴靶组织。
Structures resembling germinal centers are seen in the salivary glands of patients with Sjogren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjogren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters; The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants, These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjogren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center-type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.