PIK3IP1 Promotes Extrafollicular Class Switching in T-Dependent Immune Responses.
PIK3IP1 Promotes Extrafollicular Class Switching in T-Dependent Immune Responses.
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DOI：
10.4049/jimmunol.2000584
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发表时间：
2020-10-15
期刊：
影响因子：
--
通讯作者：
Satterthwaite AB
中科院分区：
文献类型：
--
作者：
Ottens K;Schneider J;Kane LP;Satterthwaite AB
PI 3激酶（PI 3 K）在B细胞的整个生命周期中起着多种作用。因此，其信号传递受到严格监管。这一点的重要性由以下事实说明：PI 3 K中功能突变的丧失和获得均可导致人类免疫缺陷。PIK 3 IP 1，也称为TrIP，是一种跨膜蛋白，已显示可抑制T细胞中的PI 3 K。ImmGen联盟的结果表明，PIK 3 IP 1表达在整个B细胞发育过程中以与PI 3 K活性负相关的方式波动;然而，其在B细胞中的作用知之甚少。在这里，我们定义了PIK 3 IP 1的B细胞特异性缺失的后果。B细胞发育、基础免疫球蛋白水平和T非依赖性应答不受PIK 3 IP 1缺失的影响。然而，有一个显着的延迟，在T依赖性反应的IgG的生产，和二次反应受损。这可能是由于PIK 3 IP 1在卵泡外反应中的作用，因为生发中心形成和亲和力成熟是正常的，PIK 3 IP 1在生发中心B细胞中不明显表达。与反应早期的作用一致，PIK 3 IP 1在B细胞活化后的晚期时间点以依赖于PI 3 K的方式下调。在PIK 3 IP 1缺陷型B细胞中观察到PI 3 K通路的活化增加，这是对BCR和CD 40两者的接合或单独的CD 40的强交联的响应。总之，这些观察结果表明，PIK 3 IP 1通过在B和T细胞之间的初始相互作用期间限制PI 3 K信号传导来促进滤泡外应答。
PI3 kinase (PI3K) plays multiple roles throughout the life a B cell. As such, its signaling is tightly regulated. The importance of this is illustrated by the fact that both loss and gain of function mutations in PI3K can cause immunodeficiency in humans. PIK3IP1, also known as TrIP, is a transmembrane protein that has been shown to inhibit PI3K in T cells. Results from the ImmGen consortium indicate that PIK3IP1 expression fluctuates throughout B cell development in a manner inversely correlated with PI3K activity; however, its role in B cells is poorly understood. Here we define the consequences of B cell-specific deletion of PIK3IP1. B cell development, basal immunoglobulin levels, and T-independent responses were unaffected by loss of PIK3IP1. However, there was a significant delay in the production of IgG during T-dependent responses, and secondary responses were impaired. This is likely due to a role for PIK3IP1 in the extrafollicular response, since germinal center formation and affinity maturation were normal and PIK3IP1 is not appreciably expressed in germinal center B cells. Consistent with a role early in the response, PIK3IP1 was downregulated at late time points after B cell activation, in a manner dependent on PI3K. Increased activation of the PI3K pathway was observed in PIK3IP1-deficient B cells in response to engagement of both the BCR and CD40 or strong crosslinking of CD40 alone. Taken together, these observations suggest that PIK3IP1 promotes extrafollicular responses by limiting PI3K signaling during initial interactions between B and T cells.
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影响因子：
4.4
作者：
Andjelic, S;Hsia, C;Liou, HC
通讯作者：
Liou, HC
DOI：
10.1084/jem.20180010
发表时间：
2018-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avery DT;Kane A;Nguyen T;Lau A;Nguyen A;Lenthall H;Payne K;Shi W;Brigden H;French E;Bier J;Hermes JR;Zahra D;Sewell WA;Butt D;Elliott M;Boztug K;Meyts I;Choo S;Hsu P;Wong M;Berglund LJ;Gray P;O'Sullivan M;Cole T;Holland SM;Ma CS;Burkhart C;Corcoran LM;Phan TG;Brink R;Uzel G;Deenick EK;Tangye SG
通讯作者：
Tangye SG
影响因子：
4.4
作者：
Durand, Caylib A.;Hartvigsen, Karsten;Gold, Michael R.
通讯作者：
Gold, Michael R.
影响因子：
7.3
作者：
Farmer, Jocelyn R.;Allard-Chamard, Hugues;Pillai, Shiv
通讯作者：
Pillai, Shiv
影响因子：
5.4
作者：
Herlands, Robin A.;William, Jacqueline;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.