Finkelman F D, Katona I M, Mosmann T R, Coffman R L
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1988 Feb 15;140(4):1022-7.
The lymphokine IFN-gamma has been shown in vitro to stimulate IgG2a secretion and inhibit IgG1 and IgE secretion by LPS-activated B lymphocytes. To determine whether IFN-gamma has a similar isotype regulatory role in vivo, we studied the abilities of rIFN-gamma and a mAb to IFN-gamma to modify the isotypes of Ig secreted in mice injected with a goat antibody to mouse IgD, which by itself induces large increases in levels of serum IgG1 and IgE and a relatively small increase in serum IgG2a. Multiple injections of IFN-gamma substantially inhibited production of IgG1 and IgE, and stimulated production of IgG2a in affinity purified goat antibody specific for mouse IgD-treated mice; anti-IFN-gamma antibody blocked the effects of IFN-gamma and in fact enhanced IgG1 and IgE secretion and inhibited the IgG2a response in these mice. The role of IFN-gamma in the selection of isotypes of Ig produced in response to injection of mice with the bacterium Brucella abortus (BA) was also studied, because killed, fixed BA are known to stimulate IFN secretion and a predominantly IgG2a antibody response. Anti-IFN-gamma antibody strongly suppressed IgG2a secretion and stimulated IgG1, but not IgE, secretion in BA-immunized mice. BA suppressed IgG1 and IgE secretion and enhanced IgG2a secretion in affinity purified goat antibody specific for mouse IgD-injected mice; treatment of these mice with anti-IFN-gamma antibody reversed the effects of BA on IgG1 and IgG2a secretion, but not the suppressive effect of BA on IgE secretion. These observations demonstrate that IFN-gamma has an important and perhaps unique physiologic role in the stimulation of IgG2a secretion and in the suppression of secretion of IgG1, whereas bacterial antigens can suppress IgE secretion by other mechanisms in addition to IFN-gamma secretion.
淋巴因子γ干扰素（IFN-γ）在体外已显示可刺激LPS激活的B淋巴细胞分泌IgG2a，并抑制IgG1和IgE的分泌。为了确定IFN-γ在体内是否具有类似的同种型调节作用，我们研究了重组IFN-γ（rIFN-γ）和抗IFN-γ单克隆抗体改变注射抗小鼠IgD山羊抗体的小鼠体内分泌的Ig同种型的能力，该山羊抗体本身可使血清IgG1和IgE水平大幅升高，而血清IgG2a仅有相对较小的升高。多次注射IFN-γ可显著抑制IgG1和IgE的产生，并刺激经亲和纯化的抗小鼠IgD山羊抗体处理的小鼠产生IgG2a；抗IFN-γ抗体可阻断IFN-γ的作用，实际上还增强了这些小鼠的IgG1和IgE分泌，并抑制了IgG2a反应。还研究了IFN-γ在选择接种流产布鲁氏菌（BA）小鼠所产生的Ig同种型中的作用，因为已知经杀死、固定的BA可刺激IFN分泌以及主要产生IgG2a抗体反应。抗IFN-γ抗体强烈抑制BA免疫小鼠的IgG2a分泌，并刺激IgG1分泌，但不刺激IgE分泌。BA抑制经亲和纯化的抗小鼠IgD注射小鼠的IgG1和IgE分泌，并增强IgG2a分泌；用抗IFN-γ抗体处理这些小鼠可逆转BA对IgG1和IgG2a分泌的影响，但不能逆转BA对IgE分泌的抑制作用。这些观察结果表明，IFN-γ在刺激IgG2a分泌以及抑制IgG1分泌方面具有重要且可能独特的生理作用，而细菌抗原除了通过分泌IFN-γ外，还可通过其他机制抑制IgE分泌。
