Katona I M, Urban J F, Kang S S, Paul W E, Finkelman F D
Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1991 Jun 15;146(12):4215-21.
IL-4 has been shown to induce B lymphocytes to switch from the expression of membrane IgM to the expression of membrane IgE and to be required for the generation of primary polyclonal and secondary Ag-specific IgE responses in mice. To further define the role of IL-4 in the generation of memory IgE responses, we investigated the ability of a combination of anti-IL-4 and anti-IL-4R mAb to block the generation of secondary IgE responses induced by: 1) a second infection with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus; or 2) injection of anti-IgD antibody-primed mice with anti-IgE antibody. The latter stimulus was designed to induce intrinsic membrane IgE-expressing B cells to differentiate into IgE-secreting cells. Although the IgE responses induced by a second nematode infection were completely inhibited by the combination of anti-IL-4 and anti-IL-4R mAb, anti-IgE antibody-induced IgE responses in anti-IgD primed mice were not inhibited by these antibodies to a large degree. Additional experiments demonstrated that the anti-IgE antibody-induced memory IgE response was dependent on CD4+ T cells but did not involve the low affinity B cell Fc epsilon RII. Taken together, these observations provide evidence that IL-4 is required for virgin B lymphocytes to develop into IgE-expressing cells, but is not required for B cells that express intrinsic membrane IgE to differentiate into IgE-secreting cells in a T-dependent response. Furthermore, these data suggest that secondary IgE responses in the parasite models that we have studied develop from B cells that had not previously switched to the expression of IgE.
白细胞介素-4（IL-4）已被证明可诱导B淋巴细胞从膜IgM的表达转换为膜IgE的表达，并且是小鼠中初级多克隆和次级抗原特异性IgE反应产生所必需的。为了进一步确定IL-4在记忆性IgE反应产生中的作用，我们研究了抗IL-4和抗IL-4R单克隆抗体（mAb）联合使用阻断由以下因素诱导的次级IgE反应产生的能力：1）再次感染巴西日圆线虫或多枝细颈线虫等线虫寄生虫；或2）给用抗IgD抗体致敏的小鼠注射抗IgE抗体。后一种刺激旨在诱导内源性表达膜IgE的B细胞分化为分泌IgE的细胞。尽管抗IL-4和抗IL-4R mAb联合使用可完全抑制再次线虫感染诱导的IgE反应，但抗IgE抗体诱导的抗IgD致敏小鼠中的IgE反应在很大程度上未被这些抗体抑制。额外的实验表明，抗IgE抗体诱导的记忆性IgE反应依赖于CD4 + T细胞，但不涉及低亲和力B细胞FcεRII。综上所述，这些观察结果提供了证据，即IL-4是未成熟B淋巴细胞发育为表达IgE细胞所必需的，但在T细胞依赖性反应中，表达内源性膜IgE的B细胞分化为分泌IgE的细胞则不需要IL-4。此外，这些数据表明，我们所研究的寄生虫模型中的次级IgE反应是由先前未转换为IgE表达的B细胞产生的。
