STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination.
STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination.
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DOI：
10.4049/jimmunol.161.1.302
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发表时间：
1998-07
影响因子：
4.4
通讯作者：
L. A. Linehan;W. D. Warren;P. Thompson;M. Grusby;M. T. Berton
中科院分区：
文献类型：
--
作者：
L. A. Linehan;W. D. Warren;P. Thompson;M. Grusby;M. T. Berton
生殖系C γ 1和C γ IG基因的转录被认为是同种型分别转换为IgG 1和IgE的必要先决条件。IL-4刺激和CD 40的连接可各自独立地诱导小鼠B细胞中低水平的生殖系γ 1和γ 2转录。这些信号一起协同作用以促进高水平的生殖系转录，并且通常是T依赖性同种型转换为IgG 1和IgE所需的。STAT 6转录因子在IL-4诱导的生殖系C γ 1和C γ 2基因活化中起关键作用。为了直接评估STAT 6在IL-4 R和CD 40介导的生殖系转录和转换中的作用，我们分析了来自STAT 6缺陷小鼠的脾B细胞中的这些事件。我们的研究结果表明，IL-4不诱导可检测水平的生殖细胞γ 1或转录本在STAT 6缺陷B细胞。单独由CD 40刺激诱导的种系转录表达不受影响，但CD 40和IL-4 R介导的信号之间的协同作用被完全消除。通过消化-环化PCR测量，在用CD 40配体加IL-4刺激的STAT 6缺陷型B细胞中，S γ 1的开关重组显著减少。类似地，在用IL-4、IL-5和与葡聚糖缀合的抗IgD抗体刺激的STAT 6缺陷型B细胞中，生殖系γ 1转录物表达和向S γ 1的开关重组也受损，这是T非依赖性II型应答的模型。这些结果直接证明了STAT 6在IL-4介导的非转化B细胞中生殖系IG基因转录和开关重组的活化中的关键作用。
Transcription of the germline C gamma1 and C epsilon Ig genes is believed to be a necessary prerequisite for isotype switching to IgG1 and IgE, respectively. IL-4 stimulation and ligation of CD40 can each independently induce low level germline gamma1 and epsilon transcription in murine B cells. Together these signals act synergistically to promote high level germline transcription and are normally required for T-dependent isotype switching to IgG1 and IgE. The STAT6 transcription factor has been suggested to play a critical role in IL-4-induced activation of germline C gamma1 and C epsilon genes. To directly assess the role of STAT6 in IL-4R- and CD40-mediated germline transcription and switching, we have analyzed these events in splenic B cells from STAT6-deficient mice. Our results demonstrate that IL-4 does not induce detectable levels of germline gamma1 or epsilon transcripts in STAT6-deficient B cells. Germline transcript expression induced by CD40 stimulation alone is unaffected, but synergism between CD40- and IL-4R-mediated signals is completely ablated. Switch recombination to S gamma1, as measured by digestion-circularization PCR, is dramatically reduced in STAT6-deficient B cells stimulated with CD40 ligand plus IL-4. Similarly, germline gamma1 transcript expression and switch recombination to S gamma1 are also impaired in STAT6-deficient B cells stimulated with IL-4, IL-5, and anti-IgD Abs conjugated to dextran, a model for T-independent type II responses. These results directly demonstrate a critical role for STAT6 in the IL-4-mediated activation of germline Ig gene transcription and switch recombination in nontransformed B cells.