Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.
Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.
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DOI：
10.1126/scisignal.2004189
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发表时间：
2013-10-15
影响因子：
7.3
通讯作者：
DeFranco AL
中科院分区：
文献类型：
--
作者：
Wheeler ML;Dong MB;Brink R;Zhong XP;DeFranco AL
B 细胞抗原受体 (BCR) 下游的信号传导受到严格调节，使细胞能够测量抗原相互作用的强度和持续时间并做出相应的反应。在这项研究中，我们询问二酰甘油激酶 (DGK) 对第二信使二酰甘油 (DAG) 的代谢是否在调节 BCR 下游第二信使信号强度方面发挥了作用。在缺乏 DGK z 的情况下，成熟滤泡 B 细胞中通过 Ras-ERK MAP 激酶途径的 BCR 信号传导阈值显着降低，导致体外和体内对抗原的过度反应。 DGK z 对 DAG 信号传导的抑制对于限制早期响应 T 不依赖性 2 型抗原和 T 细胞依赖性抗原而产生的抗体分泌细胞的数量尤其重要。此外，DGKδ 的缺陷与 T 细胞依赖性抗体反应期间增加 BCR 抗原亲和力的影响非常相似，强烈表明 DAG 信号传导的强度（可能通过 ERK 激活程度）对于将 BCR 对抗原的亲和力转化为免疫反应早期阶段产生的抗体量非常重要。
Signaling downstream of the B cell antigen receptor (BCR) is tightly regulated to allow for cells to gauge the strength and duration of antigen interactions and respond accordingly. In this study, we asked if metabolism of the second messenger diacylglycerol (DAG) by diacylglycerol kinase enzymes (DGKs) played a role in modulating the magnitude of signaling by this second messenger downstream of the BCR. In the absence of DGKζ, the threshold for BCR signaling through the Ras-ERK MAP kinase pathway was markedly reduced in mature follicular B cells, resulting in exaggerated responses to antigen in vitro and in vivo. Inhibition of DAG signaling by DGKζ was especially important for limiting the number of antibody-secreting cells generated early in response to both T-independent type 2 antigens and T cell-dependent antigens. Furthermore, deficiency in DGKζ closely resembled the effects of increasing antigen affinity for the BCR during the T cell-dependent antibody response, strongly indicating that the magnitude of DAG signaling, likely through the degree of ERK activation, is important for translating the affinity of the BCR for antigen into the amount of antibody produced during early stages of an immune response.
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影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
影响因子：
4.4
作者：
Richards, JD;Davé, SH;DeFranco, AL
通讯作者：
DeFranco, AL
影响因子：
4.4
作者：
Coughlin, JJ;Stang, SL;Stone, JC
通讯作者：
Stone, JC
DOI：
10.4049/jimmunol.0803941
发表时间：
2009-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gross AJ;Lyandres JR;Panigrahi AK;Prak ET;DeFranco AL
通讯作者：
DeFranco AL
影响因子：
4.4
作者：
Hashimoto, A;Takeda, K;Kurosaki, T
通讯作者：
Kurosaki, T