Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
B-Lymphocytes / metabolism
-
Cell Differentiation / physiology*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology
-
DNA-Binding Proteins / metabolism*
-
Immunoglobulin Heavy Chains / biosynthesis
-
Immunoglobulin Heavy Chains / genetics
-
Immunoglobulin Heavy Chains / immunology
-
Immunoglobulin M / biosynthesis
-
Immunoglobulin M / genetics
-
Immunoglobulin M / immunology
-
Interleukin-4 / metabolism
-
Interleukin-6 / metabolism
-
Mice
-
Plasma Cells / cytology
-
Plasma Cells / physiology*
-
Protein Folding
-
RNA Splicing / physiology
-
Regulatory Factor X Transcription Factors
-
Transcription Factors / genetics
-
Transcription Factors / immunology
-
Transcription Factors / metabolism*
-
X-Box Binding Protein 1
Substances
-
DNA-Binding Proteins
-
Immunoglobulin Heavy Chains
-
Immunoglobulin M
-
Interleukin-6
-
Regulatory Factor X Transcription Factors
-
Transcription Factors
-
X-Box Binding Protein 1
-
Xbp1 protein, mouse
-
Interleukin-4