Open AccessTranscription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses
Author(s) -
Hongsheng Wang,
Shweta Jain,
Peng Li,
JianXin Lin,
Jangsuk Oh,
ChenFeng Qi,
Yuanyuan Gao,
Jiafang Sun,
Tomomi Sakai,
Zohreh Naghashfar,
Sadia Abbasi,
Alexander L. Kovalchuk,
Silvia Bolland,
Stephen L. Nutt,
Warren J. Leonard,
Herbert C. Morse
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1901258116
Subject(s) - germinal center , bcl6 , irf8 , b cell , biology , transcription factor , immunoglobulin class switching , microbiology and biotechnology , gene , genetics , antibody
Significance The functions of transcription factors IRF8 and PU.1 in B cell activation and differentiation have been poorly understood due to redundancy between the family members. By usingMb1 -Cre–mediated B cell-specific deletion ofIrf8 andSpi1 (encoding PU.1), we provide evidence here that (i ) double deletion of IRF8 and PU.1 resulted in severe deficiency in follicular and germinal center B cells; (ii ) antibody affinity maturation was compromised in double-mutant mice; and (iii ) the expression of BCL6 was dependent on IRF8 and PU.1, indicating the existence of an IRF8/PU.1–BCL6 axis in the initiation phase of the germinal center response. Our data thus reveal that IRF8 and PU.1 are indispensable for the development of late-stage B cells.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom