Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells
Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells
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DOI：
10.1182/blood-2005-07-2871
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发表时间：
2006-02-01
期刊：
影响因子：
20.3
通讯作者：
Kansas, GS
中科院分区：
文献类型：
--
作者：
Fornek, JL;Tygrett, LT;Kansas, GS
Stat蛋白是潜在的细胞质转录因子，在哺乳动物发育的许多方面至关重要。在免疫系统中，STAT3在T细胞，中性粒细胞和巨噬细胞功能中具有不同的作用，但是STAT3在B细胞发育中的作用，尤其是在B细胞终末分化为分泌抗体分泌等离子体细胞中的作用，从未直接直接测试。在这项研究中，我们使用CRE/IOX系统来生成小鼠菌株，其中STAT3在B细胞谱系中有条件删除（STAT3（fl/fl）CD19（CRE/+））。 B细胞发育，周围B细胞室的建立以及基线血清抗体水平在STAT3（FL/FL）CD19（CRE/+）小鼠中不受干扰。引人注目的是，STAT3（FL/FL）CD19CRE（/+）小鼠在T依赖性（TD）IgG响应中显示出深刻的缺陷，但是正常的TD IgM，IgE和IgA响应以及TNOCTINPERTIST（TI）IgM和IgG3响应。此外，在STAT3（fl/fl）CD19（CRE/+）小鼠中，新生发中心（GC）形成，同种型切换和内存B细胞的生成（包括IgG（+）记忆细胞）都完好无损，表明需求对于STAT3，仅限于浆细胞分化。这些结果表明，在TD IgG浆细胞分化中，STAT3对STAT3具有深远的选择性作用，因此代表了调节同种型特异性末端B细胞分化的转录因子的独特示例。
Stat proteins are latent cytoplasmic transcription factors that are crucial in many aspects of mammalian development. In the immune system, Stat3 has distinct roles in T-cell, neutrophil, and macrophage function, but a role for Stat3 in B-cell development, particularly in the terminal differentiation of B cells into antibody-secreting plasma cells, has never been directly tested. In this study, we used the Cre/Iox system to generate a mouse strain in which Stat3 was conditionally deleted in the B-cell lineage (Stat3(fl/fl)CD19(Cre/+)). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3(fl/fl)CD19(cre/+) mice. Strikingly, Stat3(fl/fl)CD19cre(/+) mice displayed profound defects in T-dependent (TD) IgG responses, but normal TD IgM, IgE, and IgA responses and T-independent (TI) IgM and IgG3 responses. In addition, germinal center (GC) formation, isotype switching, and generation of memory B cells, including IgG(+) memory cells, were all intact in Stat3(fl/fl)CD19(Cre/+) mice, indicating that the requirement for Stat3 was limited to plasma cell differentiation. These results demonstrate a profound yet highly selective role for Stat3 in TD IgG plasma cell differentiation, and therefore represent a unique example of a transcription factor regulating isotype-specific terminal B-cell differentiation.