Restriction of memory B cell differentiation at the germinal center B cell positive selection stage

被引：26

作者：

Toboso-Navasa, Amparo ^{[1
]}

Gunawan, Arief ^{[1
]}

Morlino, Giulia ^{[1
]}

Nakagawa, Rinako ^{[1
]}

Taddei, Andrea ^{[1
]}

Damry, Djamil ^{[1
]}

Patel, Yash ^{[2
]}

Chakravarty, Probir ^{[3
]}

Janz, Martin ^{[4
,5
]}

Kassiotis, George ^{[2
]}

Brink, Robert ^{[6
]}

Eilers, Martin ^{[7
,8
]}

Calado, Dinis Pedro ^{[1
,9
]}

机构：

[1] Francis Crick Inst, Immun & Canc, London, England

[2] Francis Crick Inst, Retroviral Immunol, London, England

[3] Francis Crick Inst, Bioinformat & Biostat, London, England

[4] Max Delbruck Ctr Mol Med, Expt & Clin Res Ctr, Berlin, Germany

[5] Charite Univ Med Berlin, Berlin, Germany

[6] Garvan Inst Med Res, Immunol Div, Darlinghurst, NSW, Australia

[7] Univ Wurzburg, Bioctr, Theodor Boveri Inst, Wurzburg, Germany

[8] Univ Wurzburg, Bioctr, Comprehens Canc Ctr Mainfranken, Wurzburg, Germany

[9] Kings Coll London, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London, England

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2020年 / 217卷 / 07期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

CLASS SWITCH RECOMBINATION; TRANSCRIPTION FACTOR MIZ-1; PROTEIN-KINASE KINASE; PLASMA-CELL; C-MYC; AFFINITY MATURATION; CYCLE ARREST; GENE; ANTIGEN; ACTIVATION;

D O I：

10.1084/jem.20191933

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs. MYC is transiently induced in cells fated for GC expansion and plasma cell (PC) formation, so-called positively selected GC B cells. We found that these cells coexpressed MYC and MIZ1 (MYC-interacting zinc-finger protein 1 [ZBTB17]). MYC and MIZ1 are transcriptional activators; however, they form a transcriptional repressor complex that represses MIZ1 target genes. Mice lacking MYC-MIZ1 complexes displayed impaired cell cycle entry of positively selected GC B cells and reduced GC B cell expansion and PC formation. Notably, absence of MYC-MIZ1 complexes in positively selected GC B cells led to a gene expression profile alike that of MBCs and increased MBC differentiation. Thus, at the GC positive selection stage, MYC-MIZ1 complexes are required for effective GC expansion and PC formation and to restrict MBC differentiation. We propose that MYC and MIZ1 form a module that regulates GC B cell fate.

引用

页数：23

共 103 条

[1] Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5 [J].