XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells
- PMID: 19407814
- PMCID: PMC2684024
- DOI: 10.1038/emboj.2009.117
XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells
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.
Figures
Similar articles
-
XBP-1-deficient plasmablasts show normal protein folding but altered glycosylation and lipid synthesis.J Immunol. 2009 Sep 15;183(6):3690-9. doi: 10.4049/jimmunol.0900953. Epub 2009 Aug 26. J Immunol. 2009. PMID: 19710472 Free PMC article.
-
The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells.Mol Immunol. 2008 Feb;45(4):1035-43. doi: 10.1016/j.molimm.2007.07.029. Epub 2007 Sep 5. Mol Immunol. 2008. PMID: 17822768 Free PMC article.
-
High rate of antibody secretion is not integral to plasma cell differentiation as revealed by XBP-1 deficiency.J Immunol. 2012 Oct 1;189(7):3328-38. doi: 10.4049/jimmunol.1201042. Epub 2012 Aug 27. J Immunol. 2012. PMID: 22925926
-
The X-box binding protein-1 transcription factor is required for plasma cell differentiation and the unfolded protein response.Immunol Rev. 2003 Aug;194:29-38. doi: 10.1034/j.1600-065x.2003.00057.x. Immunol Rev. 2003. PMID: 12846805 Review.
-
Regulatory mechanisms that determine the development and function of plasma cells.Annu Rev Immunol. 2003;21:205-30. doi: 10.1146/annurev.immunol.21.120601.141138. Epub 2001 Dec 19. Annu Rev Immunol. 2003. PMID: 12524387 Review.
Cited by
-
Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.J Immunol. 2024 Aug 1;213(3):384-393. doi: 10.4049/jimmunol.2300616. J Immunol. 2024. PMID: 38864663
-
Gene module reconstruction elucidates cellular differentiation processes and the regulatory logic of specialized secretion.bioRxiv [Preprint]. 2023 Dec 29:2023.12.29.573643. doi: 10.1101/2023.12.29.573643. bioRxiv. 2023. PMID: 38234833 Free PMC article. Preprint.
-
Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation.Front Immunol. 2023 Feb 7;14:1081121. doi: 10.3389/fimmu.2023.1081121. eCollection 2023. Front Immunol. 2023. PMID: 36825019 Free PMC article.
-
Control of immune cell function by the unfolded protein response.Nat Rev Immunol. 2023 Sep;23(9):546-562. doi: 10.1038/s41577-023-00838-0. Epub 2023 Feb 8. Nat Rev Immunol. 2023. PMID: 36755160 Review.
-
Loss of AID exacerbates the malignant progression of CLL.Leukemia. 2022 Oct;36(10):2430-2442. doi: 10.1038/s41375-022-01663-5. Epub 2022 Aug 30. Leukemia. 2022. PMID: 36042317 Free PMC article.
References
-
- Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht BD (2007) XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell 27: 53–66 - PubMed
-
- Boes M, Esau C, Fischer MB, Schmidt T, Carroll M, Chen J (1998) Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J Immunol 160: 4776–4787 - PubMed
-
- Bordier C (1981) Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem 256: 1604–1607 - PubMed
-
- Brunsing R, Omori-Fitzpatrick S, Weber F, Bicknell AA, Friend L, Rickert R, Niwa M (2008) B and T cell development both involve activity of the unfolded protein response pathway. J Biol Chem 283: 17954–17961 - PubMed
-
- Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415: 92–96 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases