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


ABSTRACT: 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.

SUBMITTER: Toboso-Navasa A 

PROVIDER: S-EPMC7336312 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Toboso-Navasa Amparo A   Gunawan Arief A   Morlino Giulia G   Nakagawa Rinako R   Taddei Andrea A   Damry Djamil D   Patel Yash Y   Chakravarty Probir P   Janz Martin M   Kassiotis George G   Brink Robert R   Eilers Martin M   Calado Dinis Pedro DP  

The Journal of experimental medicine 20200701 7


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 r  ...[more]

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