Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal.
Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal.
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DOI：
10.1084/jem.20200866
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发表时间：
2021-01-04
期刊：
影响因子：
--
通讯作者：
Kurosaki T
中科院分区：
文献类型：
--
作者：
Inoue T;Shinnakasu R;Kawai C;Ise W;Kawakami E;Sax N;Oki T;Kitamura T;Yamashita K;Fukuyama H;Kurosaki T
Inoue等表明，一小群mTORC 1活性较低的生发中心来源的CD 38 intBcl 6 hi/intEfnb 1+细胞有利于记忆B细胞的命运。这一人群也有较高水平的Bcl 2和表面BCR，反过来，有助于他们的生存和发展。一个仍然没有答案的问题是，是什么驱使一小部分激活的生发中心（GC）B细胞成为长寿的静止记忆B细胞。我们在此发现，一小部分mTORC 1活性较低的GC来源的CD 38 intBcl 6 hi/intEfnb 1+细胞有利于记忆B细胞的命运。组成性高mTORC 1活性导致CD 38 intBcl 6 hi/intEfnb 1+细胞形成缺陷;相反，mTORC 1活性降低导致这种记忆倾向群体相对于回收倾向群体相对富集。此外，CD 38 intBcl 6 hi/intEfnb 1+细胞具有更高水平的Bcl 2和表面BCR，这反过来有助于它们的存活和发育。我们还发现Bcl 6的下调导致Bcl 2和BCR的表达增加。考虑到T细胞帮助的强度与mTORC 1活性之间的正相关性，我们的数据表明了一种模型，其中来自T细胞的弱帮助以及提供增加的存活信号是GC B细胞采用记忆B细胞命运的关键。
Inoue et al. show that a small population of germinal center–derived CD38intBcl6hi/intEfnb1+ cells with lower mTORC1 activity favors a memory B cell fate. This population also has higher levels of Bcl2 and surface BCR that, in turn, contributes to their survival and development. A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells to become long-lived quiescent memory B cells. We found here that a small population of GC-derived CD38intBcl6hi/intEfnb1+ cells with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38intBcl6hi/intEfnb1+ cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone population over the recycling-prone one. Furthermore, the CD38intBcl6hi/intEfnb1+ cells had higher levels of Bcl2 and surface BCR that, in turn, contributed to their survival and development. We also found that downregulation of Bcl6 resulted in increased expression of both Bcl2 and BCR. Given the positive correlation between the strength of T cell help and mTORC1 activity, our data suggest a model in which weak help from T cells together with provision of an increased survival signal are key for GC B cells to adopt a memory B cell fate.
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影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
影响因子：
3.5
作者：
Motohashi K
通讯作者：
Motohashi K
DOI：
10.1084/jem.20161263
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Inoue T;Shinnakasu R;Ise W;Kawai C;Egawa T;Kurosaki T
通讯作者：
Kurosaki T
影响因子：
32.4
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
通讯作者：
Cyster JG
影响因子：
32.4
作者：
Boothby M;Rickert RC
通讯作者：
Rickert RC