Shparago N, Zelazowski P, Jin L, McIntyre T M, Stuber E, Peçanha L M, Kehry M R, Mond J J, Max E E, Snapper C M
Walter Reed Army Medical Center, Washington, DC 20307, USA.
Int Immunol. 1996 May;8(5):781-90. doi: 10.1093/intimm/8.5.781.
A role for IL-10 in regulating Ig isotype switching directly at the level of the murine B cell has not been previously reported. In this report we show that IL-10 selectively up-regulated IgM to IgG3 class switching in lipopolysaccharide (LPS)-activated cultures through a direct effect on membrane (m) IgM+IgG3(-)B cells in vitro. IL-10 stimulated a 3- to 4-fold enhancement (from 6-8 to 20-30%) in membrane mIgG3(+) cells and a significant increase in Smu-Sgamma3 DNA rearrangement events as measured by digestion-circularization PCR (DC-PCR) over that observed with LPS alone. IL-10 induction of switching to IgG3 was not accompanied by a corresponding increase in the steady-state levels of germline CHgamma3 RNA. By contrast, IL-10 strongly inhibited the transforming growth factor-beta-mediated generation of mIgA+ cells and Smu-Salpha DNA rearrangement events in LPS-, but not CD40 ligand (CD40L)-activated B cells. This effect was not accompanied by changes in the steady-state levels of germline CHalpha RNA. IL-10 had no effect on IL-4-mediated switching to either IgG1 or IgE in either LPS- or CD40L-activated B cells. Thus, IL-10 can either enhance or suppress switching to particular murine Ig isotypes but it differs from most other murine cytokines in that its effects on switching do not appear to be associated with changes in the corresponding steady-state levels of germline CH RNA.
白细胞介素-10（IL-10）在小鼠B细胞水平直接调节免疫球蛋白（Ig）同种型转换的作用此前尚未见报道。在本报告中，我们表明，IL-10通过对体外膜（m）IgM+IgG3（-）B细胞的直接作用，在脂多糖（LPS）激活的培养物中选择性地上调IgM向IgG3的类别转换。与单独使用LPS相比，IL-10刺激膜mIgG3（+）细胞增加了3至4倍（从6-8%增至20-30%），并且通过消化-环化聚合酶链反应（DC-PCR）检测到Smu-Sgamma3 DNA重排事件显著增加。IL-10诱导向IgG3的转换并未伴随着种系CHgamma3 RNA稳态水平的相应增加。相比之下，IL-10强烈抑制转化生长因子-β介导的LPS激活而非CD40配体（CD40L）激活的B细胞中mIgA+细胞的产生和Smu-Salpha DNA重排事件。这种作用并未伴随着种系CHalpha RNA稳态水平的变化。IL-10对LPS或CD40L激活的B细胞中IL-4介导的向IgG1或IgE的转换均无影响。因此，IL-10可以增强或抑制向特定小鼠Ig同种型的转换，但它与大多数其他小鼠细胞因子不同，其对转换的影响似乎与相应种系CH RNA的稳态水平变化无关。
