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

The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers.
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DOI:
10.1038/s41590-017-0035-5
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发表时间:
2018-03
期刊:
影响因子:
30.5
通讯作者:
Turner M
Turner M
中科院分区:
医学1区
文献类型:
--
作者:
Monzón-Casanova E;Screen M;Díaz-Muñoz MD;Coulson RMR;Bell SE;Lamers G;Solimena M;Smith CWJ;Turner M

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抗体亲和力成熟发生在生发中心(GC),其中B细胞在亮区(LZ)和暗区之间循环。在LZ GC中,携带对抗原具有最高亲和力的免疫球蛋白的B细胞接收来自T辅助细胞的阳性选择信号,这促进了它们的快速增殖。在这里,我们表明,RNA结合蛋白PTBP 1是必要的GC B细胞的进展,通过细胞周期的晚期S期和亲和力成熟。PTBP 1是在接受T细胞帮助的GC B细胞中诱导的c-MYC依赖性基因程序的适当表达所必需的,并且直接调节在阳性选择期间增加的转录物的可变剪接和丰度以促进增殖。
Antibody affinity maturation occurs in germinal centres (GC) 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 T helper cells that promotes their rapid proliferation. Here we show that the RNA binding protein PTBP1 is necessary for the progression of GC B cells through late S-phase of the cell cycle and for affinity maturation. PTBP1 is required for the proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulates the alternative splicing and abundance of transcripts increased during positive selection to promote proliferation.
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