Sartoris S, Tosi G, De Lerma Barbaro A, Cestari T, Accolla R S
Institute of Immunology and Infectious Diseases, University of Verona, Italy.
Eur J Immunol. 1996 Oct;26(10):2456-60. doi: 10.1002/eji.1830261028.
In this study the genetic control of major histocompatibility complex (MHC) class II gene expression during the transition from B cell to plasma cell has been analyzed. Class II molecules are not expressed in plasma cells because of an active suppression resulting in the abrogation of class II gene transcription. We show here that the plasma cell-specific repressor function, designated SIR (suppressor of immune response genes), does not act directly on the transcription of class II genes, but instead on the transcription of the AIR-1 gene, whose product, the class II transactivator (CIITA), is fundamental for the regulation of the constitutive and inducible expression of MHC class II genes. This was unambiguously demonstrated by the fact that plasmacytoma x B cell hybrids carrying an AIR-1 locus derived from CIITA-expressing cells do not express CIITA-specific transcripts. Transfection of a cDNA containing the human CIITA coding sequence under the control of an heterologous promoter restores expression of human MHC class II genes in the hybrids and is responsible for de novo expression of mouse MHC class II genes in both the mouse plasmacytoma cell line and the hybrids. These results confirm and extend the notion of the functional conservation of the AIR-1 gene product across species barriers. Interestingly, in CIITA-transfected cell hybrids, cell surface expression of the human HLA-DQ heterodimer was not observed. This result was not attributable to lack of HLA-DQ alpha or -DQ beta transcription, because both transcripts were present in the CIITA-transfected hybrids, although at reduced levels. These findings further support our previous observations on the distinct regulation of expression of the human HLA-DQ class II subset, which may be thus controlled at the posttranscriptional level by a CIITA-independent mechanism.
在本研究中，分析了B细胞向浆细胞转变过程中主要组织相容性复合体（MHC）II类基因表达的遗传控制。由于存在主动抑制导致II类基因转录被废除，II类分子在浆细胞中不表达。我们在此表明，浆细胞特异性阻遏物功能，称为SIR（免疫反应基因阻遏物），并不直接作用于II类基因的转录，而是作用于AIR-1基因的转录，其产物II类反式激活因子（CIITA）对于MHC II类基因组成型和诱导型表达的调节至关重要。携带源自表达CIITA细胞的AIR-1基因座的浆细胞瘤x B细胞杂种不表达CIITA特异性转录本，这一事实明确证明了这一点。在异源启动子控制下转染包含人CIITA编码序列的cDNA可恢复杂种中人MHC II类基因的表达，并负责在小鼠浆细胞瘤细胞系和杂种中小鼠MHC II类基因的从头表达。这些结果证实并扩展了AIR-1基因产物跨物种屏障功能保守性的概念。有趣的是，在CIITA转染的细胞杂种中，未观察到人类HLA-DQ异二聚体的细胞表面表达。这一结果并非由于缺乏HLA-DQα或-DQβ转录，因为在CIITA转染的杂种中两种转录本均存在，尽管水平降低。这些发现进一步支持了我们之前关于人类HLA-DQ II类亚群表达独特调节的观察结果，其可能因此在转录后水平由一种不依赖CIITA的机制控制。
