Microvilli structures on B lymphocytes: inducible functional domains?
Microvilli structures on B lymphocytes: inducible functional domains?
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DOI：
10.1093/intimm/dxh031
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Severinson, E
中科院分区：
文献类型：
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作者：
Greicius, G;Westerberg, L;Severinson, E
在免疫反应过程中，B淋巴细胞和T细胞之间的互动接触对于它们的扩张是必要的。已有研究表明，B淋巴细胞从T细胞获得信号，如IL-4和CD40的交联物，这对其分化是至关重要的。我们以前发现，这些因素诱导B细胞上微绒毛的形成，这与B淋巴细胞同型黏附增加有关。在这项研究中，我们研究了IL-4是否诱导蛋白质分离到微绒毛和脂筏。我们利用免疫电子显微镜分析了参与B-T细胞共激活的分子在细胞表面的分布。用蔗糖梯度离心法分析对洗涤剂抗性膜组分的吸收。我们发现微绒毛富含ICAM-1和MHC-II类分子。而LFA-1和CD40在光滑的细胞表面更为丰富，而B7-2(CD86)则呈随机分布。我们还发现，使用β-甲基环糊精去除胆固醇后，微绒毛的数量减少，这表明它们的表达需要完整的脂筏。此外，脂多糖(LPS)激活B淋巴细胞可诱导脂筏标志物GM(1)的表达增加。然而，无论是内毒素还是内毒素+IL-4刺激的B淋巴细胞，表面和总GM(1)的表达水平相似，但在内毒素+IL-4刺激的B淋巴细胞中，GM(1)主要表达在微绒毛上。综上所述，我们的结果表明，微绒毛代表着不同的可诱导的膜域，可以通过细胞表面受体的分组和三维呈现来调节细胞与细胞的直接相互作用。
Interactive contact between B lymphocytes and T cells is necessary for their expansion during an immune response. It has been shown that B lymphocytes receive signals from T cells, such as IL-4 and cross-linking of CD40, which are crucial for their differentiation. We previously found that these factors induce formation of microvilli on B cells and that this was correlated with increased homotypic adhesion of B lymphocytes. In this study we have investigated if IL-4 induce segregation of proteins to microvilli and lipid rafts. Using immuno-electron microscopy we analyzed cell-surface distribution of molecules involved in B-T cell co-activation. Recruitment to detergent-resistant membrane fractions was analyzed using sucrose gradient centrifugation. We found that microvilli were enriched in ICAM-1 and MHC class II molecules. In contrast, LFA-1 and CD40 were more abundant on the smooth cell surfaces, while B7-2 (CD86) was randomly distributed. We also discovered that depletion of cholesterol, using beta-methyl-cyclodextrin, lowered the number of microvilli, indicating that intact lipid rafts are required for their expression. Moreover, activation of B lymphocytes by lipopolysaccharide (LPS) induced increased expression of GM(1), a marker for lipid rafts. However, although both surface and total levels of GM(1) were similar in B lymphocytes stimulated with either LPS or LPS plus IL-4, GM(1) was mainly expressed on microvilli in LPS plus IL-4-stimulated cells. Taken together, our results indicate that microvilli represent distinct inducible membrane domains that can regulate direct cell-cell interactions via grouping and three-dimensional presentation of cell-surface receptors.