NFATc2 (NFAT1) assists BCR-mediated anergy in anti-insulin B cells.
NFATc2 (NFAT1) assists BCR-mediated anergy in anti-insulin B cells.
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DOI：
10.1016/j.molimm.2014.01.003
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发表时间：
2014-12
影响因子：
3.6
通讯作者：
Kendall PL
中科院分区：
文献类型：
--
作者：
Bonami RH;Wolfle WT;Thomas JW;Kendall PL
NFAT转录因子在T和B淋巴细胞应答的激活和抑制中起关键作用。为了了解NFATc 2（NFAT 1）在维持抗胰岛素B细胞耐受性中的作用，将功能失活的NFATc 2（NFATc 2 −/−）引入具有无反应性抗胰岛素125 Tg B细胞的C57 BL/6小鼠中。抗胰岛素B细胞的产生和外周成熟为滤泡和边缘区亚群并不因功能性NFATc 2的缺乏而改变。表面B细胞受体的表达水平，重要的紧张性信号和无反应性改变，没有改变任何脾B细胞亚群。抗胰岛素抗体水平在125 Tg/B6/NFATc 2 −/−小鼠中没有差异，抗胰岛素应答在T细胞依赖性免疫后保持沉默。然而，针对体外增殖的研究表明，125 Tg B细胞的无反应性状态在125 Tg/B6/NFATc 2 −/− B细胞中响应于BCR刺激而缓解。相比之下，在用抗CD 40刺激后，125 Tg/B6/NFATc 2 −/− B细胞中不释放无反应性。125 Tg/B6/NFATc 2 −/− B细胞对BCR刺激无反应性的缓解与NFATc 1和NFATc 3的转录增加相关，而这些NFAT的表达在抗IgM刺激的125 Tg/B6/NFATc 2 +/+ B细胞中没有变化。这些数据表明，NFATc 2通过抑制其他NFAT家族成员的转录，在维持对BCR刺激的无反应性中起着微妙和选择性的作用。
NFAT transcription factors play critical roles in both the activation and repression of T and B lymphocyte responses. To understand the role of NFATc2 (NFAT1) in the maintenance of tolerance for anti-insulin B cells, functionally inactive NFATc2 (NFATc2−/−) was introduced into C57BL/6 mice that harbor anergic anti-insulin 125Tg B cells. The production and peripheral maturation of anti-insulin B cells into follicular and marginal zone subsets was not altered by the absence of functional NFATc2. Surface B cell receptor expression levels, important for tonic signaling and altered by anergy, were not altered in any spleen B cell subset. The levels of anti-insulin antibodies were not different in 125Tg/B6/NFATc2−/− mice and the anti-insulin response remained silenced following T cell dependent immunization. However, studies addressing in vitro proliferation reveal the anergic state of 125Tg B cells is relieved in 125Tg/B6/NFATc2−/− B cells in response to BCR stimulation. In contrast, anergy is not released in 125Tg/B6/NFATc2−/− B cells following stimulation with anti-CD40. The relief of anergy to BCR stimulation in 125Tg/B6/NFATc2−/− B cells is associated with increased transcription of both NFATc1 and NFATc3 while expression of these NFATs does not change in anti-IgM stimulated 125Tg/B6/NFATc2+/+ B cells. The data suggest that NFATc2 plays a subtle and selective role in maintaining anergy for BCR stimulation by repressing the transcription of other NFAT family members.
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影响因子：
64.8
作者：
KECK, K
通讯作者：
KECK, K
DOI：
10.4049/jimmunol.0803121
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Henry RA;Acevedo-Suárez CA;Thomas JW
通讯作者：
Thomas JW
影响因子：
64.5
作者：
Macián, F;García-Cózar, F;Rao, A
通讯作者：
Rao, A
影响因子：
4.4
作者：
Acevedo-Suarez, Carlos A.;Kilkenny, Dawn M.;Thomas, James W.
通讯作者：
Thomas, James W.
影响因子：
4.4
作者：
Henry-Bonami, Rachel A.;Williams, Jonathan M.;Thomas, James W.
通讯作者：
Thomas, James W.