Restriction of memory B cell differentiation at the germinal center B cell positive selection stage
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Amparo Toboso-Navasa Arief Gunawan Giulia Morlino Rinako Nakagawa Andrea Taddei Djamil Damry Yash Patel Probir Chakravarty Martin Janz George Kassiotis Robert Brink Martin Eilers Dinis CaladoAbstract
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.
Journal details
Journal Journal of Experimental Medicine
Volume 217
Issue number 7
Pages e20191933
Publication date
Full text links
Publisher website (DOI) 10.1084/jem.20191933
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Europe PubMed Central 32407433
Pubmed 32407433