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| Item Type: | Article |
|---|---|
| Title: | Restriction of memory B cell differentiation at the germinal center B cell positive selection stage |
| Creators Name: | 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. and Calado, D.P. |
| 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. |
| Keywords: | B-Lymphocytes, Cell Cycle, Cell Differentiation, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Cytidine Deaminase, Germinal Center, Immunologic Memory, Knockout Mice, Protein Binding, Protein Inhibitors of Activated STAT, Proto-Oncogene Proteins c-myc, Ubiquitin-Protein Ligases, Up-Regulation, Animals, Mice |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 217 |
| Number: | 7 |
| Page Range: | e20191933 |
| Date: | 6 July 2020 |
| Official Publication: | https://doi.org/10.1084/jem.20191933 |
| PubMed: | View item in PubMed |
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