Xu L, Rothman P
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Int Immunol. 1994 Apr;6(4):515-21. doi: 10.1093/intimm/6.4.515.
Cytokines have the ability to regulate the isotypes of antibodies produced during an immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-gamma has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to epsilon through its ability to specifically induce germline epsilon transcripts. Germline epsilon transcription appears to target class-switch recombination to the epsilon locus. However, the mechanism by which IFN-gamma inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-gamma and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-gamma suppresses the IL-4 induction of germline epsilon transcripts. In transient transfection assays, the IL-4 induction of transcription imparted by the minimal 179 bp germline epsilon promoter is repressed by IFN-gamma. Utilizing a digestion circularization-polymerase chain reaction assay we show that IL-4 induces switch recombination to epsilon, while IFN-gamma suppresses switch recombination to epsilon. These studies support a model that, through their differential effects on a cis-controlling element that regulates germline epsilon transcription, IL-4 and IFN-gamma are able to modulate B cell switch recombination to epsilon in a coordinated manner.
细胞因子具有调节免疫应答过程中产生的抗体同种型的能力。例如，已证明白细胞介素-4（IL-4）可诱导B细胞产生IgE，而干扰素-γ（IFN-γ）则可抑制这种诱导作用。最近的研究表明，IL-4似乎通过其特异性诱导胚系ε转录本的能力来诱导向ε的类别转换。胚系ε转录似乎将类别转换重组靶向到ε基因座。然而，IFN-γ抑制IL-4诱导IgE的机制尚不清楚。我们假设IFN-γ和IL-4可能对B细胞分化的同一阶段具有拮抗作用。Northern印迹分析表明，IFN-γ抑制IL-4诱导的胚系ε转录本。在瞬时转染试验中，IFN-γ可抑制由最小的179 bp胚系ε启动子赋予的IL-4转录诱导作用。利用消化环化-聚合酶链反应试验，我们表明IL-4诱导向ε的转换重组，而IFN-γ抑制向ε的转换重组。这些研究支持了一种模型，即通过它们对调节胚系ε转录的顺式控制元件的不同作用，IL-4和IFN-γ能够以协调的方式调节B细胞向ε的转换重组。
