title: XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation.
abstract: The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Shaffer
authors.forename: Miriam
authors.initials: M
authors.lastname: Shapiro-Shelef
authors.forename: Neal N
authors.initials: NN
authors.lastname: Iwakoshi
authors.forename: Ann-Hwee
authors.initials: AH
authors.lastname: Lee
authors.forename: Shu-Bing
authors.initials: SB
authors.lastname: Qian
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hurt
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Petroulakis
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: Kathryn
authors.initials: K
authors.lastname: Calame
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells; D001402:B-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D015388:Organelles / Q000502:physiology* / Q000648:ultrastructure; D010950:Plasma Cells / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C513258:Prdm1 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1