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恶性浆细胞系表达功能性CD28分子。

Malignant plasma cell lines express a functional CD28 molecule.

作者信息

Zhang X G, Olive D, Devos J, Rebouissou C, Ghiotto-Ragueneau M, Ferlin M, Klein B

机构信息

Institute of Molecular Genetics, Unit for Cellular Therapy, Hôpital Saint Eloi, Montpellier, France.

出版信息

Leukemia. 1998 Apr;12(4):610-8. doi: 10.1038/sj.leu.2400971.

Abstract

The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells.

摘要

对人骨髓瘤细胞系(HMCL)恶性浆细胞上存在的CD28分子的功能进行了研究。首先,骨髓瘤细胞表达的CD28抗原密度与正常T细胞相似。骨髓瘤CD28分子能够结合B7-Ig分子以及转染了B7-1 cDNA的L细胞,抗CD28单克隆抗体可抑制这种结合。骨髓瘤细胞不表达B7-1抗原,但表达低密度的B7-2抗原。两个HMCL的骨髓瘤B7-2分子能够结合CTLA-4蛋白。由于未发现PI-3激酶的p85亚基与CD28分子的自发结合,因此无法证明存在自分泌的CD28:B7-2激活。此外,阻断性抗CD28单克隆抗体不影响HMCL的IL-6依赖性或自主性增殖。有或没有佛波酯(TPA)刺激时,骨髓瘤CD28分子的激活均不影响骨髓瘤细胞的增殖、存活、分化、激活抗原和细胞因子受体的表达或细胞因子的产生。然而,如先前在T细胞CD28分子中所示,B7-1转染细胞触发骨髓瘤CD28分子会导致PI-3激酶的p85亚基与CD28分子结合。这种能够结合B7分子的高密度CD28分子的表达可能有助于下调骨髓瘤细胞的免疫控制。

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