Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus
Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus
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DOI：
10.1002/art.20519
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发表时间：
2004-10-01
影响因子：
--
通讯作者：
Kroczek, RA
中科院分区：
文献类型：
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作者：
Hutloff, A;B端chner, K;Kroczek, RA
Objective.在系统性红斑狼疮（SLE）中，记忆B细胞和浆细胞的产生增加导致自身免疫性高丙种球蛋白血症和肾脏中破坏性免疫球蛋白沉积。我们进行了这项研究，以确定驱动这种过度激活的B细胞区室，这是在SLE的中心问题的生物学机制。我们用流式细胞术分析了SLE患者外周血B细胞上T细胞特异性诱导共刺激分子（ICOS）及其配体（ICOS-L）的表达。我们使用一组大的表面抗原将ICOS-L表达与B细胞的分化状态相关联。此外，我们还对SLE患者的肾脏进行了免疫组化分析。我们发现SLE患者CD 4+和CD 8 + T细胞上ICOS的表达增加。同时，我们记录了高比例的外周血记忆B细胞上ICOS-L的下调。基于体外实验，我们推断这种ICOS-L在B细胞上的下调是最近与ICOS+ T细胞在体内相互作用的标志。在SLE患者的肾脏中，我们发现B细胞和浆细胞与ICOS+ T细胞紧密接触。对ICOS-L下调的B细胞的详细分析表明，ICO是驱动SLE中记忆B细胞和浆细胞形成的力量之一。此外，我们在肾脏中T细胞-B细胞相互作用区域中的浆细胞的鉴定表明T细胞驱动的B细胞活化过程的组分可能发生在SLE的外周组织中。
Objective. In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.Methods. We used flow cytometry to analyze expression of the T cell-specific inducible costimulator (ICOS) and its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE patients. We correlated ICOS-L expression with the differentiation status of the B cells using a large panel of surface antigens. In addition, SLE kidneys were analyzed by immunohistology.Results. We found an increased expression of ICOS on CD4+ as well as CD8+ T cells in SLE. At the same time, we documented a down-regulation of ICOS-L on a high proportion of peripheral blood memory B cells. Based on in vitro experiments, we inferred that this ICOS-L down-regulation on B cells was a signature of recent interaction with ICOS+ T cells in vivo. In the kidneys of SLE patients, we found clusters of B cells and plasma cells in close contact with ICOS+ T cells.Conclusion. Detailed analysis of B cells with down-regulated ICOS-L suggests that ICO is one of the forces driving the formation of memory B cells and plasma cells in SLE. Furthermore, our identification of plasma cells in areas of T cell-B cell interaction in kidneys suggests that components of a T cell-driven B cell activation process may take place in peripheral tissues in SLE.