Selective regulation of mature IgG1 transcription by CD86 and β2-adrenergic receptor stimulation
Selective regulation of mature IgG1 transcription by CD86 and β2-adrenergic receptor stimulation
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DOI：
10.4049/jimmunol.170.10.5143
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Sanders, VM
中科院分区：
文献类型：
--
作者：
Podojil, JR;Sanders, VM
CD86和β(2)-肾上腺素能受体(β(2)AR)单独或共同刺激B细胞，可增加CD40配体/IL-4激活的B细胞产生的IgG1蛋白水平。已知CD40和IL-4R刺激B细胞增加IgG1蛋白水平的机制是通过增加生殖系Gamma1转录、IgG1类转换和成熟的IgG1转录，而介导CD86和β(2)AR诱导的效应的分子机制尚不清楚。在本研究中，我们使用实时荧光定量聚合酶链式反应显示CD40配体/IL-4激活的B细胞在CD86和/或β(2)AR刺激下成熟的IgG1转录水平增加，并且这种增加反映了IgG1蛋白的增加。此外，我们发现CD86和/或β(2)AR诱导的成熟IgG1转录增加是由于核连续分析确定的成熟IgG1转录速度的增加。当两种受体都受到刺激时，这种作用是相加的，当使用CD86和β(2)AR缺陷小鼠的B细胞时，这种作用就会消失。相反，生殖系的Gamma1转录水平、成熟的IgG1转录本的稳定性、IgG1阳性的B细胞数量和分泌IgG1的B细胞数量没有变化。这些结果首次证明CD86和/或β(2)AR对CD40配体/IL-4激活的B细胞的刺激通过增加成熟的IgG1转录速率来增加每个细胞产生的IgG1蛋白水平。
Stimulation of CD86 and the beta(2)-adrenergic receptor(beta(2)AR) on a B cell, either alone or together, is known to increase the level of IgG1 protein produced by a CD40 ligand/IL-4-activated B cell. It is also known that the mechanism by which CD40 and IL-4R stimulation on a B cell increases the level of IgG1 protein is by increasing germline gamma1 transcription, IgG1 class switching, and mature IgG1 transcription, while the molecular mechanism responsible for mediating the CD86- and beta(2)AR-induced effect remains unknown. In the present study using real-time PCR we show that the level of mature IgG1 transcription increases in CD40 ligand/IL-4-activated B cells following stimulation of either CD86 and/or beta(2)AR, and that this increase reflects the increase in IgG1 protein. Furthermore, we show that the CD86- and/or beta(2)AR-induced increase in mature IgG1 transcript is due to an increase in the rate of mature IgG1 transcription, as determined by nuclear run-on analysis. This effect is additive when both receptors are stimulated and is lost when B cells from CD86- and beta(2)AR-deficient mice are used. In contrast, the level of germline gamma1 transcription, the stability of mature IgG1 transcript, the number of IgG1-positive B cells, and the number of IgG1-secreting B cells did not change. These results provide the first evidence that CD86 and/or beta(2)AR stimulation on a CD40 ligand/IL-4-activated B cell increases the level of IgG1 protein produced per cell by increasing the rate of mature IgG1 transcription.