XBP1 Governs Late Events in Plasma Cell Differentiation and Is not Required for Antigen-Specific Memory B Cell Development

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XBP1 Governs Late Events in Plasma Cell Differentiation and Is not Required for Antigen-Specific Memory B Cell Development

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dc.contributor.author McHeyzer-Williams, Louise J.
dc.contributor.author Kowal, Czeslawa
dc.contributor.author Lee, Ann-Hwee
dc.contributor.author Volpe, Bruce T.
dc.contributor.author Diamond, Betty
dc.contributor.author McHeyzer-Williams, Michael G.
dc.contributor.author Todd, Derrick James
dc.contributor.author Glimcher, Laurie Hollis
dc.date.accessioned 2011-12-23T02:15:03Z
dc.date.issued 2009
dc.identifier.citation Todd, Derrick J., Louise J. McHeyzer-Williams, Czeslawa Kowal, Ann-Hwee Lee, Bruce T. Volpe, Betty Diamond, Michael G. McHeyzer-Williams, and Laurie H. Glimcher. 2009. XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. Journal of Experimental Medicine 206(10): 2151-2159. en_US
dc.identifier.issn 0022-1007 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978623
dc.description.abstract The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1fl/fl CD19+/cre conditional knockout (XBP1CD19) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1CD19 mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1CD19 mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment. en_US
dc.language.iso en_US en_US
dc.publisher Rockefeller University Press en_US
dc.relation.isversionof doi:10.1084/jem.20090738 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757870/pdf/ en_US
dash.license LAA
dc.title XBP1 Governs Late Events in Plasma Cell Differentiation and Is not Required for Antigen-Specific Memory B Cell Development en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Journal of Experimental Medicine en_US
dash.depositing.author Todd, Derrick James
dc.date.available 2011-12-23T02:15:03Z
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases Immunology en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases TPH en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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