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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.

Type Journal
ISBN 1540-9538 (Electronic) 0022-1007 (Linking)
Authors Toboso-Navasa, A.; Gunawan, A.; Morlino, G.; Nakagawa, R.; Taddei, A.; Damry, D.; Patel, Y.; Chakravarty, P.; Janz, M.; Kassiotis, G.; Brink, R.; Eilers, M.; Calado, D. P.
Responsible Garvan Author Prof Robert Brink
Publisher Name JOURNAL OF EXPERIMENTAL MEDICINE
Published Date 2020-07-06
Published Volume 217
Published Issue 7
Status Published in-print
DOI 10.1084/jem.20191933
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/32407433