BAFF-induced changes in B cell antigen receptor-containing lipid rafts in Sjogren's syndrome
BAFF-induced changes in B cell antigen receptor-containing lipid rafts in Sjogren's syndrome
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DOI：
10.1002/art.21478
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Youinou, P
中科院分区：
文献类型：
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作者：
d'Arbonneau, F;Pers, JO;Youinou, P
目标。目的：探讨BAFF过量产生对原发性干燥综合征（SS）患者B细胞亚群分布和功能的影响。流式细胞术分析B淋巴细胞表型。细胞膜IgD和CD38表达水平的差异被用来鉴定从初始Bm1细胞到记忆Bm5细胞进化的B淋巴细胞亚群。基于CD45RA低表达的发现，我们对Bm2/Bm2’细胞进行了分类，通过共聚焦显微镜确定了CD19分子和B细胞受体转运到脂筏中的时间过程。采用自行开发的酶联免疫吸附法测定血清BAFF水平。与风湿病对照组和正常对照组相比，原发性SS患者的“循环”Bm2/Bm2'细胞扩增。此外，这些B细胞亚群功能异常。B细胞受体在这些细胞脂筏中的长期停留与B细胞中CD19表达的升高有关，最明显的是来自原发性SS患者的Bm2和Bm2‘细胞。BAFF水平在患者中高于正常对照，并与原发性SS患者中Bm2/Bm2’细胞的百分比及其CD19表达相关。将正常对照中分选的Bm1或Bm2细胞在存在或不存在bba的情况下进行培养，证实了这些相关性。原发性SS患者的Bm2/Bm2细胞表达CD19分子多于正常对照。BAFF可能参与了CD19的表达升高。这些患者可能是BAFF拮抗剂治疗的合适人选。
Objective. To determine the effect of excessive production of BAFF on the distribution and function of B cell subsets in patients with primary Sjogren's syndrome (SS).Methods. The phenotype of B lymphocytes was analyzed by flow cytometry. Differences in the expression level of membrane IgD and CD38 were used to identify B lymphocyte subsets evolving from naive Bm1 through memory Bm5 cells. Based on our finding of a low expression of CD45RA, we sorted Bm2/Bm2' cells to determine the time course of translocation of the CD19 molecule and the B cell receptor into lipid rafts, by confocal microscopy. Serum levels of BAFF were measured by an enzyme-linked immunosorbent assay developed in-house.Results. "Circulating" Bm2/Bm2' cells were expanded in patients with primary SS compared with rheumatic disease controls and with normal controls. In addition, these B cell subsets were functionally abnormal. Prolonged residency of the B cell receptor in lipid rafts in these cells was associated with elevated CD19 expression in B cells, most notably, Bm2 and Bm2' cells, obtained from the patients with primary SS. BAFF levels were higher in the patients than in the normal controls and correlated with the percentage of Bm2/Bm2' cells and their expression of CD19 in primary SS patients. These correlations were confirmed by placing sorted Bm1 or Bm2 cells from normal controls in culture in the presence or absence of BAFF.Conclusion. Bm2/Bm2' cells express more CD19 molecules in primary SS patients than in normal controls. BAFF might participate in this elevated expression of CD19. These patients might be suitable candidates for treatment with BAFF antagonists.