Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1.
The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, providing an integral link between XBP-1, the UPR and plasma cell differentiation. Signals involved in plasma cell differentiation, specifically interleukin-4, control the transcription of XBP-1, whereas its post-transcriptional processing is dependent on synthesis of immunoglobulins during B cell differentiation. We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR.
Iwakoshi
Neal N
NN
Department of Immunology and Infectious Diseases, Harvard School of Public Health 651 Huntington Avenue, Boston, Massachusetts 02115-6017, USA.
Lee
Ann-Hwee
AH
Vallabhajosyula
Prasanth
P
Otipoby
Kevin L
KL
Rajewsky
Klaus
K
Glimcher
Laurie H
LH
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology*; D017510:Protein Folding; D012326:RNA Splicing / Q000502:physiology; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D015850:Interleukin-6; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D015847:Interleukin-4