NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
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DOI：
10.1084/jem.20100945
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发表时间：
2011-04-11
期刊：
影响因子：
--
通讯作者：
Serfling E
中科院分区：
文献类型：
--
作者：
Bhattacharyya S;Deb J;Patra AK;Thuy Pham DA;Chen W;Vaeth M;Berberich-Siebelt F;Klein-Hessling S;Lamperti ED;Reifenberg K;Jellusova J;Schweizer A;Nitschke L;Leich E;Rosenwald A;Brunner C;Engelmann S;Bommhardt U;Avots A;Müller MR;Kondo E;Serfling E
缺乏NFATc 1的小鼠B细胞表现出增殖、存活、同种型类别转换、细胞因子产生和T细胞辅助缺陷。通过研究骨髓、脾脏或生殖中心B细胞中Nfatc 1基因失活的小鼠，我们表明NFATc 1支持脾B细胞在B细胞受体（BCR）刺激后的增殖并抑制活化诱导的细胞死亡。BCR触发导致脾B细胞中NFATc 1/αA（NFATc 1的短亚型）的表达。NFATc 1消融损害了由T细胞非依赖性II型抗原诱导的IG类向IgG 3的转换，以及IgG 3+浆母细胞的形成。携带NFATc 1 −/− B细胞的小鼠具有两倍多的产生白细胞介素10的B细胞。NFATc 1 −/− B细胞在体外抑制T细胞合成干扰素-γ，这些小鼠表现出实验性自身免疫性脑脊髓炎的轻度临床过程。在很大程度上，NFATc 1 −/− B细胞的功能缺陷是由BCR诱导的Ca 2+通量减少和钙调神经磷酸酶（Cn）激活引起的。通过影响CD 22、Rcan 1、CnA和NFATc 1/αA表达，NFATc 1控制Ca 2+依赖性Cn-NFAT信号网络，从而控制BCR刺激后脾B细胞的命运。
Mouse B cells lacking NFATc1 exhibit defective proliferation, survival, isotype class switching, cytokine production, and T cell help. By studying mice in which the Nfatc1 gene was inactivated in bone marrow, spleen, or germinal center B cells, we show that NFATc1 supports the proliferation and suppresses the activation-induced cell death of splenic B cells upon B cell receptor (BCR) stimulation. BCR triggering leads to expression of NFATc1/αA, a short isoform of NFATc1, in splenic B cells. NFATc1 ablation impaired Ig class switch to IgG3 induced by T cell–independent type II antigens, as well as IgG3+ plasmablast formation. Mice bearing NFATc1−/− B cells harbor twofold more interleukin 10–producing B cells. NFATc1−/− B cells suppress the synthesis of interferon-γ by T cells in vitro, and these mice exhibit a mild clinical course of experimental autoimmune encephalomyelitis. In large part, the defective functions of NFATc1−/− B cells are caused by decreased BCR-induced Ca2+ flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/αA expression, NFATc1 controls the Ca2+-dependent Cn–NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.
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