Zelazowski P, Collins J T, Dunnick W, Snapper C M
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1995 Feb 1;154(3):1223-31.
Cytokines are believed to regulate Ig class switching, in part, through selective modulation of germ-line constant heavy (CH) gene transcription. B cell activators such as LPS or activated T cell membranes also influence germ-line CH RNA expression in the absence of exogenous cytokines. In this report we determined whether multivalent Ag receptor cross-linking, utilizing dextran-conjugated anti-IgD Abs (alpha delta-dex), could also regulate germ-line CH RNA expression. We demonstrated that alpha delta-dex markedly inhibited germ-line epsilon RNA expression, but strongly augmented germ-line gamma 1 RNA, in LPS + IL-4-stimulated cultures. This was correlated with > 90% alpha delta-dex-mediated suppression in the secretion of IgE and generation of membrane (m)IgE+ cells, and a more modest 50% reduction in IgG1 synthesis and mIgG1+ cells. Furthermore, alpha delta-dex inhibited the LPS induction of both gamma 3 and gamma 2b germ-line RNA and the associated secretion of IgG3 and IgG2b. A similar alpha delta-dex-mediated suppression of germ-line gamma 2a RNA and IgG2a secretion in LPS + IFN-gamma-stimulated cultures was observed. By contrast, activation of resting B cells with alpha delta-dex alone led to induction of germ-line gamma 3, gamma 1, and gamma 2b RNA but did not stimulate detectable expression of RNA specific for gamma 2a or epsilon. These studies demonstrate that: 1) germ-line gamma 1 gene expression is regulated uniquely, 2) germ-line transcription and switch recombination can be dissociated, 3) the germ-line transcription of each IgG isotype has an independent pattern of regulation, and 4) cross-linking of the Ag receptor, by itself, can stimulate small amounts of germ-line CH RNA.
细胞因子被认为部分通过对种系恒定重链（CH）基因转录的选择性调节来调控Ig类别转换。诸如脂多糖（LPS）或活化的T细胞膜等B细胞激活剂在没有外源性细胞因子的情况下也会影响种系CH RNA的表达。在本报告中，我们确定了利用葡聚糖偶联的抗IgD抗体（αδ-葡聚糖）进行多价抗原受体交联是否也能调节种系CH RNA的表达。我们证明，在LPS + IL-4刺激的培养物中，αδ-葡聚糖显著抑制种系εRNA的表达，但强烈增强种系γ1 RNA的表达。这与αδ-葡聚糖介导的IgE分泌和膜（m）IgE+细胞生成中> 90%的抑制相关，以及IgG1合成和mIgG1+细胞中较为适度的50%减少相关。此外，αδ-葡聚糖抑制LPS诱导的γ3和γ2b种系RNA以及相关的IgG3和IgG2b分泌。在LPS + IFN-γ刺激的培养物中观察到类似的αδ-葡聚糖介导的种系γ2a RNA和IgG2a分泌的抑制。相比之下，仅用αδ-葡聚糖激活静止B细胞会导致种系γ3、γ1和γ2b RNA的诱导，但不会刺激γ2a或ε特异性RNA的可检测表达。这些研究表明：1）种系γ1基因表达受到独特调节；2）种系转录和类别转换重组可以分离；3）每种IgG同种型的种系转录具有独立的调节模式；4）抗原受体的交联本身可以刺激少量的种系CH RNA。
