INTERLEUKIN-4 CAUSES ISOTYPE SWITCHING TO IGE IN T-CELL-STIMULATED CLONAL B-CELL CULTURES

INTERLEUKIN-4 CAUSES ISOTYPE SWITCHING TO IGE IN T-CELL-STIMULATED CLONAL B-CELL CULTURES
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DOI:
10.1084/jem.168.3.853
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发表时间:
1988-09-01
影响因子:
15.3
通讯作者:
COFFMAN, RL
COFFMAN, RL
中科院分区:
医学1区
文献类型:
--
作者:
LEBMAN, DA;COFFMAN, RL

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虽然已经确定IL-4在LPS刺激的B细胞培养物中增强IgG 1和IgE分泌,但是这些研究未能确定IL-4是否优先诱导同种型转换或优先允许成熟的预定型前体细胞。为了区分这些可能性,有必要确定IL-4对克隆扩增过程中单个前体细胞分泌的同种型的影响。因此,建立了用特异于兔IG和兔抗小鼠IgM的Th 2辅助细胞系刺激的B细胞的克隆培养物。大多数B细胞能够在这些条件下进行克隆扩增。为了改变存在的IL-4的水平,将IL-4或抗IL-4添加到培养物中。在IL-4的存在下,分泌IgE的克隆的比例增加,分泌IgM的克隆的比例减少。向培养物中加入IL-4也增加了单个克隆分泌的IgE的量。因此,这些实验明确证明IL-4在Th 2刺激的B细胞培养物中引起特异性重链类别转换为IgE。相比之下,IL-4不影响分泌IgG 1的克隆的比例,这表明Th细胞-B细胞相互作用的其他后果在IgG 1反应的产生中发挥作用。
Although it has been established that IL-4 enhances both IgG1 and IgE secretion in LPS-stimulated B cell cultures, these studies failed to determine whether IL-4 preferentially induces isotype switching or preferentially allows for the maturation precommitted precursor cells. To distinguish between these possibilites, it is necessary to ascertain the effect of IL-4 on the isotypes secreted by individual precursor cells during clonal expansion. Therefore, clonal cultures of B cells stimulated with a Th2 helper cell line specific for rabbit Ig and rabbit anti-mouse IgM were established. The majority of B cells are capable of undergoing clonal expansion under these conditions. To vary the level of IL-4 present, either IL-4 or anti-IL-4 was added to cultures. In the presence of IL-4 there was an increase in the proportion of clones that secreted IgE and a decrease in the proportion of clones that secreted IgM. The addition of IL-4 to cultures also increased the amount of IgE secreted by individual clones. Thus, these experiments definitively prove that IL-4 causes specific heavy chain class switching to IgE in Th2-stimulated B cell cultures. In contrast, IL-4 does not affect the proportion of clones secreting IgG1, suggesting that other consequences on Th cell-B cell interactions play a role in the generation of an IgG1 response.