title: The diverse roles of IRF4 in late germinal center B-cell differentiation.
abstract: Interferon regulatory factor 4 (IRF4) is a member of the IRF family of transcription factors and is expressed in most cell types of the immune system. Within the B-cell lineage, IRF4 is expressed in all developmental stages except during the germinal center (GC) reaction. IRF4 expression, however, is upregulated during exit from the GC reaction and has been demonstrated to have critical functions in at least three key developmental processes: the termination of the GC B-cell transcriptional program, immunoglobulin (Ig) class switch recombination (CSR), and plasma cell development. Herein, we attempt to reconcile the often contradictory findings regarding IRF4 into a model to explain the role of IRF4 in the transcription factor networks that operate within exiting GC B cells. In addition, a deregulation of the biological programs controlled by IRF4 has recently been implicated in the pathogenesis of various B-cell-derived malignancies. Determining the specific functions of IRF4 in the markedly diverse developmental processes that coordinate B-cell development is therefore likely to have important implications for understanding these malignancies and devising therapeutic interventions.
authors.affiliation: Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
authors.forename: Nilushi S
authors.initials: NS
authors.lastname: De Silva
authors.forename: Giorgia
authors.initials: G
authors.lastname: Simonetti
authors.forename: Nicole
authors.initials: N
authors.lastname: Heise
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4