A model integrating tonic and antigen-triggered BCR signals to predict the survival of primary B cells.
A model integrating tonic and antigen-triggered BCR signals to predict the survival of primary B cells.
复制标题
整合强直和抗原触发的 BCR 信号来预测原代 B 细胞存活的模型
DOI：
10.1038/s41598-017-13993-x
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发表时间：
2017-11-02
影响因子：
4.6
通讯作者：
Wang JY
中科院分区：
文献类型：
--
作者：
Yasuda S;Zhou Y;Wang Y;Yamamura M;Wang JY
在缺乏外源性抗原结合的情况下，BCR构成性地传递“补品”生存信号。然而，强直性BCR信号的强度及其与抗原触发的生存信号的关系尚不清楚。我们发现，与表达低水平BCR的原代B细胞相比，表达高水平BCR的原代B细胞具有升高的BCR强直信号和增加的存活率。此外，我们发现低剂量的F（ab’）2 α-IgM抗体与BCR交联后，B细胞存活率不但没有增强，反而降低，只有当BCR大部分被F（ab’）2 α-IgM抗体占据时，B细胞存活率才会增强。基于这些实验结果，我们提出了一个整合补品和抗原触发的BCR信号的数学模型。我们的模型表明，交联BCR产生的信号强度是自由BCR产生的强直信号的4.3倍，并且B细胞激活的阈值对应于61%的表面BCR交联产生的信号。该模型还可以根据B细胞的初始BCR水平和抗原刺激的强度和持续时间预测B细胞的存活概率，符合B细胞耐受的机制。
The BCR constitutively transmits a “tonic” survival signal in the absence of exogenous antigen-binding. However, the strength of tonic BCR signal and its relationship with antigen-triggered survival signal are poorly understood. We found that primary B cells expressing high levels of BCR had elevated BCR tonic signal and increased survival compared with those expressing low levels of BCR. In addition, we found that crosslinking BCR with low doses of F(ab′)2 α-IgM antibodies did not enhance, but rather decreased, B cell survival and that only when most of the BCR were occupied by F(ab′)2 α-IgM antibodies was B cell survival enhanced. Based on these experimental results, we present a mathematical model integrating tonic and antigen-triggered BCR signals. Our model indicates that the signal generated from crosslinked BCR is 4.3 times as strong as the tonic signal generated from free BCR and that the threshold of B cell activation corresponds to the signal generated by crosslinking 61% of the surface BCR. This model also allows the prediction of the survival probability of a B cell based on its initial BCR level and the strength and duration of antigen stimulation, and fits with the mechanism of B cell tolerance.
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影响因子：
4.6
作者：
Shinohara H;Inoue K;Yumoto N;Nagashima T;Okada-Hatakeyama M
通讯作者：
Okada-Hatakeyama M
影响因子：
64.8
作者：
Duehren-von Minden, Marcus;Uebelhart, Rudolf;Jumaa, Hassan
通讯作者：
Jumaa, Hassan
影响因子：
56.9
作者：
OKeefe, TL;Williams, GT;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
64.5
作者：
Kraus, M;Alimzhanov, MB;Rajewsky, K
通讯作者：
Rajewsky, K
影响因子：
4.4
作者：
Ouchida, Rika;Kurosaki, Tomohiro;Wang, Ji-Yang
通讯作者：
Wang, Ji-Yang