期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 1, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200866
关键词
-
资金
- JSPS KAKENHI [JP17K08882, JP26221306, JP19H01028]
- SENSHIN Medical Research Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Astellas Foundation for Research on Metabolic Disorders
This study found that GC-derived CD38(int)Bcl6(hi/int)Efnb1(center dot) cells with lower mTORC1 activity are more likely to become memory B cells, with higher levels of Bcl2 and BCR contributing to their survival and development. Weak T cell help and increased survival signals are key factors for GC B cells to adopt a memory B cell fate.
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 CD38(int)Bcl6(hi/int)Efnb1(center dot) cells with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38(int)Bcl6(hi/int)Efnb1(center dot) cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone population over the recycling-prone one. Furthermore, the CD38(int)Bcl6(hi/int)Efnb1(center dot) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据