Snapper C M, Rosas F, Moorman M A, Jin L, Shanebeck K, Klinman D M, Kehry M R, Mond J J, Maliszewski C R
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Int Immunol. 1996 Jun;8(6):877-85. doi: 10.1093/intimm/8.6.877.
IFN-gamma has been shown to either stimulate or inhibit Ig secretion. No studies have yet addressed the basis for these seemingly conflicting properties nor whether IFN-gamma acted directly at the level of the B cell to mediate its effects. Thus, we studied the ability of IFN-gamma to regulate Ig secretion in sort-purified, resting murine B cells that were >99% Ig+, activated either through membrane Ig using unconjugated or dextran-conjugated anti-IgD antibodies (alphadelta-dex) or through CD40 using soluble or membrane CD40 ligand (CD40L). B cells activated with alphadelta-dex proliferated but do not secrete Ig, even in the presence of IL-1 + IL-2. We demonstrate that IFN-gamma only when added subsequent to B cell stimulation with alphadelta-dex, but not unconjugated anti-IfD antibody, plus IL-1 + IL-2 induces up to 100-fold enhancements in Ig secretion and in the numbers of Ig-secreting cells. The predominant Ig isotype secreted is IgM, with IgG3 and IgG2a comprising the majority of non-IgM antibody. IFN-gamma must act in concert with IL-2 for stimulation of Ig secretion. Further, IFN-gamma synergizes with IL-3 + granulocyte-macrophage colony stimulating factor for induction of Ig synthesis. IFN-gamma also enhances IgA syntheses by transforming growth factor-beta-induced membrane IgA+ cells. By contrast, 125IIFN-gamma fails to stimulate Ig secretion in B cells activated with CD40L in the presence or absence of IL-1 + IL-2 or IL-4. However, the combination of CD40L and alphabeta-dex is strongly synergistic for IFN-gamma-induced Ig secretion. Thus, these data establish that IFN-gamma can act directly on the B cell to induce Ig synthesis without the participation of any other cell and demonstrates that the mode of activation of the B cell plays an important role in directing the action of IFN-gamma.
γ干扰素已被证明既能刺激也能抑制免疫球蛋白（Ig）的分泌。尚未有研究探讨这些看似相互矛盾的特性的基础，也未涉及γ干扰素是否直接在B细胞水平发挥作用以介导其效应。因此，我们研究了γ干扰素调节分选纯化的静息小鼠B细胞中Ig分泌的能力，这些B细胞Ig阳性率>99%，通过使用未偶联或葡聚糖偶联的抗IgD抗体（αδ-葡聚糖）通过膜Ig激活，或通过使用可溶性或膜型CD40配体（CD40L）通过CD40激活。用αδ-葡聚糖激活的B细胞增殖但不分泌Ig，即使在存在白细胞介素-1 +白细胞介素-2的情况下也是如此。我们证明，γ干扰素仅在B细胞用αδ-葡聚糖刺激后添加时，而不是在用未偶联的抗IgD抗体加白细胞介素-1 +白细胞介素-2刺激后添加时，可诱导Ig分泌和分泌Ig的细胞数量增加高达100倍。分泌的主要Ig同种型是IgM，IgG3和IgG2a构成了大多数非IgM抗体。γ干扰素必须与白细胞介素-2协同作用以刺激Ig分泌。此外，γ干扰素与白细胞介素-3 +粒细胞-巨噬细胞集落刺激因子协同作用以诱导Ig合成。γ干扰素还通过转化生长因子-β诱导的膜IgA+细胞增强IgA合成。相比之下，125Iγ干扰素在存在或不存在白细胞介素-1 +白细胞介素-2或白细胞介素-4的情况下，均不能刺激用CD40L激活的B细胞分泌Ig。然而，CD40L和αβ-葡聚糖的组合对γ干扰素诱导的Ig分泌具有强烈的协同作用。因此，这些数据表明γ干扰素可直接作用于B细胞以诱导Ig合成，无需任何其他细胞的参与，并证明B细胞的激活方式在指导γ干扰素的作用中起重要作用。
