Maffei A, Scarpellino L, Bernard M, Carra G, Jotterand-Bellomo M, Guardiola J, Accolla R S
J Immunol. 1987 Aug 1;139(3):942-8.
In a previous series of studies, we had shown that the constitutive Ia expression in an immunoselected Ia-human B cell variant, RJ 2.2.5, could be restored by somatic cell hybridization with mouse B cells. These experiments allowed us to show the existence of a transacting activator factor(s) operating across species barriers and encoded by the aIr-1 locus located on mouse chromosome 16. The aim of the present study was to investigate whether the B cell constitutive Ia expression and the inducible Ia expression, as seen in macrophages treated with IFN-gamma, are controlled by similar intracellular factors. To this purpose, we constructed an interspecies somatic cell hybrid between the human Ia-RJ 2.2.5 B cells and the mouse Ia-P388 D1 macrophage cells. These murine cells transiently express Ia antigens when incubated with IFN-gamma. Our results show that RJ 2.2.5 X P388 D1 cell hybrids do not express either human or mouse class II gene products. Treatment with human recombinant IFN-gamma did not modify the MHC phenotype of either the hybrid cells or the human parental cells. On the other hand, treatment of the hybrid cells with murine recombinant IFN-gamma resulted in de novo expression of mouse Ia mRNA and corresponding cell surface antigens without, however, reinduction of the human class II-positive phenotype. Furthermore, treatment with the mouse lymphokine significantly increased the levels of human HLA class I mRNA and corresponding cell surface antigens in the hybrid cells, further reinforcing the notion of the existence of non-species-specific secondary mediators generated after receptor-ligand interaction in the IFN-gamma system. Together, these results indicate that in macrophages, the intracellular events taking place after binding of IFN-gamma with its own receptor and leading to the expression of a class II-positive phenotype do not operate via an activation of the aIr-1 locus and/or its products. Thus, at least in our experimental system, we can firmly establish a first, relevant distinction between constitutive and inducible class II gene expression. This difference, dictated by the specific differentiation program of each cell type, may be relevant for the understanding of the function of class II gene products.
在先前的一系列研究中，我们已表明，通过与小鼠B细胞进行体细胞杂交，免疫选择的Ia - 人B细胞变体RJ 2.2.5中的组成型Ia表达能够得以恢复。这些实验使我们得以证明存在一种跨物种作用的激活因子，该因子由位于小鼠16号染色体上的aIr - 1基因座编码。本研究的目的是调查B细胞组成型Ia表达以及在用γ干扰素处理的巨噬细胞中所见的诱导型Ia表达是否受相似的细胞内因子控制。为此，我们构建了人Ia - RJ 2.2.5 B细胞与小鼠Ia - P388 D1巨噬细胞之间的种间体细胞杂种。这些鼠细胞在与γ干扰素孵育时会短暂表达Ia抗原。我们的结果显示，RJ 2.2.5×P388 D1细胞杂种既不表达人也不表达小鼠的II类基因产物。用人重组γ干扰素处理并未改变杂种细胞或人亲本细胞的MHC表型。另一方面，用鼠重组γ干扰素处理杂种细胞导致小鼠Ia mRNA和相应细胞表面抗原的从头表达，然而，人II类阳性表型并未再次诱导。此外，用小鼠淋巴因子处理显著增加了杂种细胞中人HLA I类mRNA和相应细胞表面抗原的水平，进一步强化了在γ干扰素系统中受体 - 配体相互作用后产生非物种特异性二级介质的观点。总之，这些结果表明，在巨噬细胞中，γ干扰素与其自身受体结合后发生的导致II类阳性表型表达的细胞内事件并非通过激活aIr - 1基因座和/或其产物来起作用。因此，至少在我们的实验系统中，我们可以明确确立组成型和诱导型II类基因表达之间的首个相关区别。这种由每种细胞类型的特定分化程序所决定的差异，可能与理解II类基因产物的功能相关。
