In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis.
In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis.
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DOI：
10.4049/jimmunol.1001983
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发表时间：
2011-02-01
期刊：
影响因子：
--
通讯作者：
Clark MR
中科院分区：
文献类型：
--
作者：
Chang A;Henderson SG;Brandt D;Liu N;Guttikonda R;Hsieh C;Kaverina N;Utset TO;Meehan SM;Quigg RJ;Meffre E;Clark MR
系统性红斑狼疮(SLE)最常见的严重表现是肾炎，其特征是肾小球和肾小管间质免疫复合物沉积、炎症和瘢痕形成。大量研究表明，肾小球肾炎是由于B细胞耐受性的全身性破坏，导致含有与无处不在的自身抗原反应的抗体的免疫复合体的局部沉积。然而，SLE肾小管间质疾病的发病机制尚不清楚。在此，我们证明，在68例狼疮性肾炎活检的队列中，超过一半的肾小管间质浸润物被组织成边界清楚的T：B细胞聚集体或含有滤泡树突状细胞的生发中心(GC)。对原位表达的免疫球蛋白图谱的采样显示，这两种组织学模式都与肾内B细胞克隆性扩张和正在进行的体细胞过度突变有关。而在T：B集合体中，增殖细胞为CD138+−/−浆母细胞。GCs或T：B聚集体的存在与肾小管基底膜免疫复合体密切相关。这些数据表明第三淋巴样新生在狼疮肾小管间质炎症的发病机制中起重要作用。
The most prevalent severe manifestation of systemic lupus erythematosus (SLE) is nephritis which is characterized by immune complex deposition, inflammation, and scarring in both glomeruli and in the tubulointerstitium. Numerous studies indicate that glomerulonephritis results from a systemic break in B cell tolerance resulting in the local deposition of immune complexes containing antibodies reactive with ubiquitous self-antigens. However, the pathogenesis of SLE tubulointerstitial disease is not known. Herein, we demonstrate that in over half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was organized into either well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the in situ expressed immunoglobulin 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 while in T:B aggregates, they were CD138+CD20low/− plasmablasts. The presence of either 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.
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影响因子：
32.4
作者：
Herlands, Robin A.;Christensen, Sean R.;Sweet, Rebecca A.;Hershberg, Uri;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
DOI：
10.1073/pnas.0502323102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Burgoon, MP;Keays, KM;Gilden, DH
通讯作者：
Gilden, DH
影响因子：
19.6
作者：
Adalid-Peralta, L.;Mathian, A.;Koutouzov, S.
通讯作者：
Koutouzov, S.
影响因子：
1
作者：
Hicks, John;Bullard, Daniel C.
通讯作者：
Bullard, Daniel C.