IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
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DOI：
10.4049/jimmunol.1001950
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发表时间：
2011-02-01
期刊：
影响因子：
--
通讯作者：
Morse HC 3rd
中科院分区：
文献类型：
--
作者：
Feng J;Wang H;Shin DM;Masiuk M;Qi CF;Morse HC 3rd
边缘区（MZ）和卵泡（FO） B细胞发育的转录控制仍不完全清楚。转录因子IFN调节因子（IRF）8在早期B细胞的分化中起重要作用。在本文中，我们证明了IRF8也是MZ和FO B细胞正常发育所必需的。常规敲除Irf8 （Irf8 - / -）或在Irf8的IRF关联域发生点突变的小鼠MZ B细胞数量增加。为了确定IRF8缺陷对B细胞的内在影响，我们将IRF8条件等位基因与CD19-Cre小鼠杂交（称为IRF8条件敲除[CKO]）。与对照组相比，这些小鼠的MZ增大，MZ和FO B细胞数量增加。CKO小鼠FO B细胞CD23表达降低，CD21表达适度升高。基因表达谱显示，IRF8-CKO小鼠B细胞产量的增加与参与转录、信号传导和炎症调节的基因表达变化有关。功能研究表明，IRF8-CKO小鼠对t非依赖型和t依赖性Ags产生正常的Ab反应。因此，IRF8控制MZ和FO B细胞的扩增和成熟，但对B细胞功能的影响很小。
Transcriptional control of marginal zone (MZ) and follicular (FO) B cell development remains incompletely understood. The transcription factor, IFN regulatory factor (IRF)8, is known to play important roles in the differentiation of early B cells. In this article, we demonstrate that IRF8 is also required for normal development of MZ and FO B cells. Mice with a conventional knockout of Irf8 (IRF8–/–) or a point mutation in the IRF association domain of IRF8 had increased numbers of MZ B cells. To determine the B cell-intrinsic effects of IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with CD19-Cre mice (designated IRF8-conditional knockout [CKO]). These mice had enlarged MZ and increased numbers of MZ and FO B cells compared with controls. The FO B cells of CKO mice exhibited reduced expression of CD23 and moderately increased expression of CD21. Gene-expression profiling showed that increased B cell production in IRF8-CKO mice was associated with changes in expression of genes involved in regulation of transcription, signaling, and inflammation. Functional studies showed that IRF8-CKO mice generated normal Ab responses to T-independent and T-dependent Ags. Thus, IRF8 controls the expansion and maturation of MZ and FO B cells but has little effect on B cell function.
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影响因子：
4.4
作者：
Qi, Chen-Feng;Li, Zhaoyang;Raffeld, Mark;Wang, Hongsheng;Kovalchuk, Alexander L.;Morse, Herbert C., III
通讯作者：
Morse, Herbert C., III
脾脏中的B细胞发育发生在离散的步骤中，并取决于B细胞受体衍生的信号的质量。
影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
影响因子：
20.3
作者：
Guo, Feng;Weih, Debra;Weih, Falk
通讯作者：
Weih, Falk
影响因子：
32.4
作者：
Cariappa, A;Tang, M;Pillai, S
通讯作者：
Pillai, S
影响因子：
20.3
作者：
Polli, M;Dakic, A;Nutt, SL
通讯作者：
Nutt, SL