Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B antigen-presenting cell interactions.
Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B antigen-presenting cell interactions.
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DOI：
10.1084/jem.179.5.1507
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发表时间：
1994-05-01
期刊：
影响因子：
--
通讯作者：
Kupfer A
中科院分区：
文献类型：
--
作者：
Kupfer H;Monks CR;Kupfer A
抗原(Ag)特异性辅助性T细胞(Th)通过分泌细胞因子和表达激活受体(如gp39)来调节Ag特异性B细胞的增殖和分化。在体外，细胞因子和激活受体以一种非抗原特异性的方式发挥作用。因此，目前尚不清楚在生理Th-B细胞相互作用中，抗原特异性是如何影响B细胞反应的。在此，我们在单细胞水平上研究了克隆的Th细胞与小的脾B细胞之间的相互作用，小B细胞是Th细胞的抗原提呈细胞。Th-B细胞结合物的数字共聚焦免疫荧光显微镜显示了这些相互作用的分子和细胞性质的显著变化，尽管该系统中的所有相互作用都被认为是抗原特异性的。孵育30h后，B细胞开始分裂，这一过程完全依赖于Th细胞和Ag的存在。免疫荧光显微镜观察显示，所有有丝分裂B细胞基本上都与Th细胞结合，并面向IL-4高度集中的Th细胞的微管组织中心(MTOC)。其他与相同Th细胞结合但不靠近Th-MTOC的B细胞仍处于间期。这些结果提供了第一个直接的结构和功能证据，证明B细胞和Th细胞的相互作用位置影响他们的免疫反应。我们认为，在Ag诱导的Th-B细胞相互作用中，面向Th-MTOC的B细胞优先增殖，因为它们是局部分泌细胞因子的受体。此外，这些B细胞可能与新表达的受体相互作用，这些受体也可能局部插入Th膜。激活分子向Th结合的APC的极化传递可能会对原本不是抗原特异性的效应器分子施加功能特异性。
Antigen (Ag)-specific T helper (Th) cells regulate the proliferation and differentiation of Ag-specific B cells by secreting cytokines and by expressing activating receptors like gp39. In vitro, the cytokines and the activating receptors function in an Ag-nonspecific manner. It is unclear, therefore, how Ag specificity is imposed on B cell responses in physiological Th-B cell interactions. Here we studied, at the single cell level, the interactions between cloned Th cells and small splenic B cells, which served as Ag-specific antigen-presenting cells (APCs) to the Th cells. Digital confocal immunofluorescence microscopy of Th-B cell conjugates revealed significant variability in the molecular and cellular properties of these interactions, in spite of the fact that all the interactions in this system were expected to be Ag specific. After 30 h of incubation B cells began to divide, and this process was entirely dependent on the presence of both Th cells and Ag. Immunofluorescence microscopic studies showed that essentially all the mitotic B cells were bound to Th cells and faced the microtubule organizing center (MTOC) in the Th cells where interleukin 4 was highly concentrated. Other B cells that were bound to the same Th cells but were not close to the Th-MTOC remained in interphase. These results provide the first direct structural and functional evidence that the site of interaction of B cells with Th cells affects their immune response. We propose that, during Ag-induced Th-B cell interactions, B cells that are bound facing the Th-MTOC proliferate preferentially because they are the recipients of locally secreted cytokines. In addition, these B cells may interact with newly expressed receptors, which may also be locally inserted into the Th membrane. The polarized delivery of activating molecules towards the Th-bound APCs may impose functional specificity on effector molecules that otherwise are not Ag specific.
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DOI：
10.1084/jem.165.6.1565
发表时间：
1987-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kupfer A;Swain SL;Singer SJ
通讯作者：
Singer SJ
影响因子：
5.4
作者：
OWENS, T
通讯作者：
OWENS, T
影响因子：
5.4
作者：
RIEDEL, C;OWENS, T;NOSSAL, GJV
通讯作者：
NOSSAL, GJV
DOI：
10.1073/pnas.84.16.5888
发表时间：
1987-08-01
影响因子：
11.1
作者：
KUPFER, A;SINGER, SJ;SWAIN, SL
通讯作者：
SWAIN, SL
DOI：
10.1073/pnas.88.3.775
发表时间：
1991-02-01
影响因子：
11.1
作者：
KUPFER, A;MOSMANN, TR;KUPFER, H
通讯作者：
KUPFER, H