Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.
Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.
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DOI：
10.1084/jem.174.5.1179
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发表时间：
1991-11-01
期刊：
影响因子：
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通讯作者：
Gause WC
中科院分区：
文献类型：
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作者：
Finkelman FD;Svetic A;Gresser I;Snapper C;Holmes J;Trotta PP;Katona IM;Gause WC
刺激小鼠体内干扰素α(IFN-α)产生的抗原和感染因子诱导主要是免疫球蛋白(Ig)G2a同种型并且含有很少或不含IgE的抗体应答。这表明 IFN-α 可能在指导 Ig 同种型选择中发挥作用。与这种可能性相一致的是，我们发现给小鼠注射重组小鼠IFN-α可抑制IgE分泌，增强IgG2a分泌，并且对用外来抗IgD抗体刺激的小鼠中的IgG1分泌没有独立影响。给小鼠注射聚肌苷酸。聚胞苷酸（poly I.C），一种巨噬细胞IFN-α产生的诱导剂，也能抑制抗IgD抗体诱导的IgE反应并刺激IgG2a反应；这些效应可被中和小鼠 IFN-α/β 的绵羊抗体阻断。在抗 IgD 抗体诱导的免疫反应早期注射时，重组 IFN-α 和 Poly I.C 均具有最大的 IgE 抑制和 IgG2a 刺激作用。在用脂多糖 (LPS) + 白细胞介素 4 (IL-4) 培养的小鼠 B 细胞中添加 IFN-α 可抑制 IgG1 和 IgE 的产生，但效果远不如 IFN-gamma。 IFN-α抑制抗IgD抗体诱导的脾脏IL-4 mRNA水平的增加，但增强抗IgD抗体诱导的脾脏IFN-γ mRNA水平的增加。这些结果与 IFN-α 对小鼠 Ig 同种型表达的影响一致，因为 IL-4 刺激 IgE 并抑制 IgG2a 分泌，而 IFN-γ 则发挥相反的作用。这些观察结果表明，抗原呈递细胞通过在免疫反应过程的早期分泌 IFN-α，可以通过直接影响 B 细胞和影响 T 细胞的分化来影响免疫反应的性质。
Antigens and infectious agents that stimulate interferon alpha(IFN- alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN- alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.