Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
J Immunol. 2011 Feb 1;186(3):1849-60. doi: 10.4049/jimmunol.1001983. Epub 2010 Dec 27.
The most prevalent severe manifestation of systemic lupus erythematosus is nephritis, which is characterized by immune complex deposition, inflammation, and scarring in glomeruli and the tubulointerstitium. Numerous studies indicated that glomerulonephritis results from a systemic break in B cell tolerance, resulting in the local deposition of immune complexes containing Abs reactive with ubiquitous self-Ags. However, the pathogenesis of systemic lupus erythematosus tubulointerstitial disease is not known. In this article, we demonstrate that in more than half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was organized into well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the in situ-expressed Ig repertoire revealed that both histological patterns were associated with intrarenal B cell clonal expansion and ongoing somatic hypermutation. However, in the GC histology, the proliferating cells were CD138(-)CD20(+) centroblasts, whereas they were CD138(+)CD20(low/-) plasmablasts in T:B aggregates. The presence of GCs or T:B aggregates was strongly associated with tubular basement membrane immune complexes. These data implicate tertiary lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation.
系统性红斑狼疮最常见的严重表现是肾炎，其特征是免疫复合物沉积、炎症和肾小球及肾小管间质瘢痕形成。许多研究表明，肾小球肾炎是由于 B 细胞耐受的系统性破坏，导致含有与普遍自身抗原反应的 Abs 的免疫复合物在局部沉积。然而，系统性红斑狼疮肾小管间质疾病的发病机制尚不清楚。在本文中，我们证明在 68 例狼疮肾炎活检的一半以上的队列中，肾小管间质浸润被组织成界限清楚的 T:B 细胞聚集或包含滤泡树突状细胞的生发中心（GC）。原位表达的 Ig 库的取样表明，两种组织学模式都与肾内 B 细胞克隆扩增和持续的体细胞超突变有关。然而，在 GC 组织学中，增殖细胞是 CD138(-)CD20(+) 中心母细胞，而在 T:B 聚集物中则是 CD138(+)CD20(low/-) 浆母细胞。GC 或 T:B 聚集物的存在与管状基底膜免疫复合物强烈相关。这些数据提示三级淋巴样组织发生在狼疮肾小管间质炎症的发病机制中。
