The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers

被引:63
|
作者
Monzon-Casanova, Elisa [1 ,2 ]
Screen, Michael [1 ]
Diaz-Munoz, Manuel D. [1 ]
Coulson, Richard M. R. [1 ]
Bell, Sarah E. [1 ]
Lamers, Greta [1 ]
Solimena, Michele [3 ,4 ,5 ,6 ,7 ]
Smith, Christopher W. J. [2 ]
Turner, Martin [1 ]
机构
[1] Babraham Inst, Lab Lymphocyte Signaling & Dev, Cambridge, England
[2] Univ Cambridge, Dept Biochem, Cambridge, England
[3] Tech Univ Dresden, Univ Hosp, Mol Diabetol, Dresden, Germany
[4] Tech Univ Dresden, Fac Med, Dresden, Germany
[5] Tech Univ Dresden, Paul Langerhans Inst Dresden, Helmholtz Ctr Munich, Univ Hosp, Dresden, Germany
[6] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany
[7] German Ctr Diabet Res DZD eV, Neuherberg, Germany
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
C-MYC; AFFINITY MATURATION; DYNAMIC REGULATION; CENTER LIGHT; EXPRESSION; REGULATOR; KINASE; GENE; PROLIFERATION; TRANSLATION;
D O I
10.1038/s41590-017-0035-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation.
引用
收藏
页码:267 / +
页数:21
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