NDLI: XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells

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XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells

Content Provider	Semantic Scholar
Author	Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Love, J. Christopher Ploegh, Hidde L.
Copyright Year	2009
Abstract	XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies.
Starting Page	1624
Ending Page	1636
Page Count	13
File Format	PDF HTM / HTML
DOI	10.1038/emboj.2009.117
PubMed reference number	19407814
Journal	Medline
Volume Number	28
Alternate Webpage(s)	http://dspace.mit.edu/bitstream/handle/1721.1/74263/Ploegh_XBP-1%20regulates.pdf?sequence=1
Alternate Webpage(s)	http://ftp.ncbi.nlm.nih.gov/pub/pmc/37/5a/emboj2009117a.PMC2684024.pdf
Alternate Webpage(s)	http://embojnl.embopress.org/content/embojnl/28/11/1624.full.pdf
Alternate Webpage(s)	http://emboj.embopress.org/content/embojnl/28/11/1624/DC7/embed/inline-supplementary-material-7.pdf?download=true
Alternate Webpage(s)	http://dspace.mit.edu/openaccess-disseminate/1721.1/74263
Alternate Webpage(s)	https://doi.org/10.1038/emboj.2009.117
Journal	The EMBO journal
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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