Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 116 (2019-05-07), Heft 19, S. 9511-9520
Online
academicJournal
Zugriff:
The IRF and Ets families of transcription factors regulate the expression of a range of genes involved in immune cell development and function. However, the understanding of the molecular mechanisms of each family member has been limited due to their redundancy and broad effects on multiple lineages of cells. Here, we report that double deletion of floxed IrfS and Spi1 (encoding PU.1) by Mb1-Cre (designated DKO mice) in the B cell lineage resulted in severe defects in the development of follicular and germinal center (GC) B cells. Class-switch recombination and antibody affinity maturation were also compromised in DKO mice. RNA-seq (sequencing) and ChIP-seq analyses revealed distinct IRF8 and PU.1 target genes in follicular and activated B cells. DKO B cells had diminished expression of target genes vital for maintaining follicular B cell identity and GC development. Moreover, our findings reveal that expression of B-cell lymphoma protein 6 (BCL6), which is critical for development of germinal center B cells, is dependent on IRF8 and PU.1 in vivo, providing a mechanism for the critical role for IRF8 and PU.1 in the development of GC B cells. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses.
|
---|---|
Autor/in / Beteiligte Person: | Wang, Hongsheng ; Jain, Shweta ; Li, Peng ; Lin, Jian-Xin ; Oh, Jangsuk ; Qi, Chenfeng ; Gao, Yuanyuan ; Sun, Jiafang ; Sakai, Tomomi ; Naghashfar, Zohreh ; Abbasi, Sadia ; Kovalchuk, Alexander L. ; Bolland, Silvia ; Nutt, Stephen L. ; Leonard, Warren J. ; Morse III, Herbert C. |
Link: | |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 116 (2019-05-07), Heft 19, S. 9511-9520 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.1901258116 |
Schlagwort: |
|
Sonstiges: |
|