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Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription

The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultu...

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Detalles Bibliográficos
Autores principales: Ubieta, Kenia, Garcia, Mireia, Grötsch, Bettina, Uebe, Steffen, Weber, Georg F., Stein, Merle, Ekici, Arif, Schett, Georg, Mielenz, Dirk, Bozec, Aline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502419/
https://www.ncbi.nlm.nih.gov/pubmed/28566276
http://dx.doi.org/10.1084/jem.20160514
Descripción
Sumario:The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultures revealed a reduced differentiation from large pre–B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2–deficient B cells. Moreover, expression of IL7Rα and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro–B cell proliferation and small pre–B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2–deficient pro–B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages.