title: Dynamic changes in Id3 and E-protein activity orchestrate germinal center and plasma cell development.
abstract: The generation of high-affinity antibodies requires germinal center (GC) development and differentiation of long-lived plasma cells in a multilayered process that is tightly controlled by the activity of multiple transcription factors. Here, we reveal a new layer of complexity by demonstrating that dynamic changes in Id3 and E-protein activity govern both GC and plasma cell differentiation. We show that down-regulation of Id3 in B cells is essential for releasing E2A and E2-2, which in a redundant manner are required for antigen-induced B cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors, including Blimp1, Xbp1, and CXCR4, and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Renee
authors.initials: R
authors.lastname: Gloury
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zotos
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Malou
authors.initials: M
authors.lastname: Zuidscherwoude
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Frederick
authors.initials: F
authors.lastname: Masson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liao
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jhaguaral
authors.initials: J
authors.lastname: Hasbold
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Phil D
authors.initials: PD
authors.lastname: Hodgkin
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia kallies@wehi.edu.au.
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000276:immunology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D051796:Inhibitor of Differentiation Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019718:Receptors, CXCR4; D000073940:Transcription Factor 4; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C514936:CXCR4 protein, mouse; C513258:Prdm1 protein, mouse; C075668:Tcf3 protein, mouse; C090743:Tcf4 protein, mouse; C000605544:Xbp1 protein, mouse; C067679:Idb3 protein, mouse