文章：

骨髓瘤细胞和树突状细胞递呈微生物抗原后，通过骨髓瘤细胞- Th2细胞相互作用介导的骨髓瘤发展增强

Enhancement of myeloma development mediated though myeloma cell-Th2 cell interactions after microbial antigen presentation by myeloma cells and DCs

原文发布日期：2012-06-15

DOI: 10.1038/bcj.2012.19

类型: Original Article

开放获取: 是

英文摘要：

Microbial agents are regarded as a potential cause of tumors, but their direct effects on tumors, such as myeloma, are not well studied. Our studies demonstrated that expression of HLA-DR and CD40 on the myeloma cell membrane surface is upregulated by interferon-γ and/or microbial antigens (Ags). Unlike prior studies, our study showed that Th2 cells cannot promote myeloma growth directly. However, Bacillus Calmette–Guerin Vaccine (BCGV)-specific Th2 cells stimulated by BCGV-loaded dendritic cells (DCs) promoted myeloma clonogenicity directly when the myeloma cells expressed major histocompatibility complex Class-II molecules (MHC-II) and took up BCGV Ag. B-cell lymphoma 6 (Bcl-6) protein expression and the proportion of HLA-DR+ or CD40+ cells were higher in colonies of Th2 cell-stimulated myeloma cells. Furthermore, anti-HLA-DR or neutralizing CD40 antibody could prevent this increase in Bcl-6 expression and colony number. These results indicate that microbes and microbial Ag-specific Th2 cells may directly impact the biology of myeloma and contribute to tumor progression. Activation may be limited to MHC-II+ myeloma cells that retain B cell and stem cell characteristics. Taken together, our data suggest that factors involved in microbial Ag presentation, such as DCs, Th2 cells and so on, are potential targets for myeloma therapeutic intervention.

摘要翻译： 

微生物制剂被视为肿瘤的潜在诱因，但它们对骨髓瘤等肿瘤的直接作用尚未得到充分研究。我们的研究证明，干扰素-γ和/或微生物抗原可上调骨髓瘤细胞膜表面HLA-DR和CD40的表达。与既往研究不同，本研究发现Th2细胞不能直接促进骨髓瘤生长。然而，当骨髓瘤细胞表达主要组织相容性复合体II类分子并摄取卡介苗抗原时，经卡介苗负载的树突状细胞刺激的卡介苗特异性Th2细胞可直接促进骨髓瘤克隆形成。在Th2细胞刺激的骨髓瘤细胞集落中，B细胞淋巴瘤6蛋白表达水平及HLA-DR阳性或CD40阳性细胞比例更高。此外，抗HLA-DR抗体或CD40中和抗体可阻止Bcl-6表达及集落数量的增加。这些结果表明微生物及微生物抗原特异性Th2细胞可能直接影响骨髓瘤的生物学特性并促进肿瘤进展。这种激活作用可能仅限于保留B细胞和干细胞特性的MHC-II阳性骨髓瘤细胞。综上所述，我们的研究提示参与微生物抗原呈递的因素（如树突状细胞、Th2细胞等）可作为骨髓瘤治疗干预的潜在靶点。

原文链接：

Enhancement of myeloma development mediated though myeloma cell-Th2 cell interactions after microbial antigen presentation by myeloma cells and DCs