Karupiah G, Sacks T E, Klinman D M, Fredrickson T N, Hartley J W, Chen J H, Morse H C
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Virology. 1998 Jan 5;240(1):12-26. doi: 10.1006/viro.1997.8900.
The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First flow cytometric analysis revealed that surface expression of CD45R, IgM, and IgK by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG2a. Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4+ T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced following infection with MCMV, but only IL-6 and IFN-gamma proteins were detectable by ELISA. In addition, the numbers of cells producing IL-6 and IFN-gamma were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the absence of IFN-gamma, surface expression and serum levels of IgG2a were reduced while IgG1 expression was increased.
本研究结果表明，小鼠巨细胞病毒（MCMV）在初次感染的急性期可诱导小鼠多克隆B细胞活化。首先，流式细胞术分析显示，MCMV感染小鼠脾细胞表面CD45R、IgM和IgK的表达显著降低，同时表面表达IgG的细胞频率增加。其次，ELIspot分析表明，流式细胞术揭示的变化与产生IgG的细胞数量增加相平行，尤其是分泌IgG2a的细胞。第三，MCMV感染动物产生的IgG抗体可与多种自身和外来抗原发生反应。MCMV诱导的B细胞活化不依赖于CD4+T细胞介导的辅助和CD40，因为在两种缺乏该T细胞亚群的小鼠模型和缺乏CD40的小鼠中均观察到了活化。逆转录-聚合酶链反应分析表明，感染MCMV后，细胞因子IL-6、IL-10和IFN-γ的mRNA转录本迅速被诱导，但通过ELISA仅可检测到IL-6和IFN-γ蛋白。此外，脾脏中产生IL-6和IFN-γ的细胞数量显著增加。在IL-6缺陷小鼠中，多克隆B细胞活化反应的强度降低了50%，但在缺乏IFN-γ的小鼠中并未降低。在缺乏IFN-γ的情况下，IgG2a的表面表达和血清水平降低，而IgG1表达增加。
