XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation.
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.
Shaffer
A L
AL
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Shapiro-Shelef
Miriam
M
Iwakoshi
Neal N
NN
Lee
Ann-Hwee
AH
Qian
Shu-Bing
SB
Zhao
Hong
H
Yu
Xin
X
Yang
Liming
L
Tan
Bruce K
BK
Rosenwald
Andreas
A
Hurt
Elaine M
EM
Petroulakis
Emmanuel
E
Sonenberg
Nahum
N
Yewdell
Jonathan W
JW
Calame
Kathryn
K
Glimcher
Laurie H
LH
Staudt
Louis M
LM
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
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