Purkerson J M, Isakson P C
Department of Pharmacology, University of Virginia Medical School, Charlottesville 22908.
J Exp Med. 1992 Apr 1;175(4):973-82. doi: 10.1084/jem.175.4.973.
We have examined the contributions of Interleukin 4 (IL-4), IL-5, and other stimuli to the expression of Immunoglobulin G1 (IgG1) and IgE in murine B lymphoblasts activated with anti-Ig. The combination of IL-4 and -5 induced B lymphoblasts to proliferate and to secrete IgM and IgG1. However, an additional stimulus was required along with IL-4 and -5 for induction of IgE secretion. This stimulus was provided by lipopolysaccharides (LPS) or cytokines produced by TC-1 or EL4 cells. In the absence of IL-5, exceptionally high concentrations of IL-4 (greater than 1,000 U/ml) were required to elicit IgG1 and IgE secretion from B lymphoblasts cultured with either LPS or TC-1-conditioned media (CM). To investigate regulation of expression of gamma 1 and epsilon genes by IL-4, -5, and LPS, the requirements for induction of gamma 1 and epsilon germline and productive transcripts were examined. Germline gamma 1, but not epsilon, transcripts were detected in RNA from B lymphoblasts treated with IL-4 and -5 for 48 h. In contrast, both germline gamma 1 and epsilon transcripts could be detected in B lymphoblasts cultured with IL-4 and LPS, and steady state levels of germline gamma 1 transcripts were four- to sevenfold higher in blasts cultured with LPS and IL-4, compared with blasts cultured with IL-4 and -5. LPS enhanced steady state levels of germline transcripts induced by IL-4, but LPS did not promote substantial accumulation of productive gamma 1 and epsilon transcripts. In contrast, IL-5 did not affect steady state levels of germline transcripts stimulated by IL-4, but did markedly increase levels of productive gamma 1 and epsilon transcripts. Thus, lymphokines regulate two distinct events in isotype switching: induction of germline transcripts (IL-4), and production of VDJ-C gamma 1 and VDJ-C epsilon mRNA (IL-5), which leads to secretion of IgG1 and IgE.
我们研究了白细胞介素4（IL-4）、IL-5及其他刺激因素对用抗Ig激活的小鼠B淋巴母细胞中免疫球蛋白G1（IgG1）和IgE表达的贡献。IL-4和-5共同作用可诱导B淋巴母细胞增殖并分泌IgM和IgG1。然而，要诱导IgE分泌，除了IL-4和-5之外还需要额外的刺激。这种刺激由脂多糖（LPS）或TC-1或EL4细胞产生的细胞因子提供。在没有IL-5的情况下，需要极高浓度的IL-4（大于1000 U/ml）才能从用LPS或TC-1条件培养基（CM）培养的B淋巴母细胞中诱导出IgG1和IgE分泌。为了研究IL-4、-5和LPS对γ1和ε基因表达的调控，我们检测了诱导γ1和ε种系及有功能转录本的条件。在用IL-4和-5处理48小时的B淋巴母细胞的RNA中检测到了种系γ1转录本，但未检测到ε转录本。相比之下，在用IL-4和LPS培养的B淋巴母细胞中可同时检测到种系γ1和ε转录本，并且与用IL-4和-5培养的母细胞相比，用LPS和IL-4培养的母细胞中种系γ1转录本的稳态水平高4至7倍。LPS可提高IL-4诱导的种系转录本的稳态水平，但LPS不会促进有功能的γ1和ε转录本的大量积累。相反，IL-5不影响IL-4刺激的种系转录本的稳态水平，但会显著提高有功能的γ1和ε转录本的水平。因此，淋巴因子在同种型转换中调节两个不同的事件：种系转录本的诱导（IL-）和VDJ-Cγ1和VDJ-CεmRNA的产生（IL-5），这导致IgG1和IgE的分泌。
