Restriction of memory B cell differentiation at the germinal center B cell positive selection stage
Authors
- A. Toboso-Navasa
- A. Gunawan
- G. Morlino
- R. Nakagawa
- A. Taddei
- D. Damry
- Y. Patel
- P. Chakravarty
- M. Janz
- G. Kassiotis
- R. Brink
- M. Eilers
- D.P. Calado
Journal
- Journal of Experimental Medicine
Citation
- J Exp Med 217 (7): e20191933
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.