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Xbp1 governs late events in plasma cell differentiation and is not required for antigen-specific memory b cell development

Academic Article
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Overview

authors

  • Todd, D. J.
  • McHeyzer-Williams, L. J.
  • Kowal, C.
  • Lee, A. H.
  • Volpe, B. T.
  • Diamond, B.
  • McHeyzer-Williams, Michael G.
  • Glimcher, L. H.

publication date

  • September 2009

journal

  • Journal of Experimental Medicine  Journal

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 XBP1(fl/fl) CD19(+/cre) conditional knockout (XBP1(CD19)) 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 XBP1(CD19) 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 XBP1(CD19) mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment.

subject areas

  • Animals
  • B-Lymphocytes
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins
  • Immunologic Memory
  • Lupus Erythematosus, Systemic
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Mice, Inbred NZB
  • Mice, Knockout
  • Plasma Cells
  • Syndecan-1
  • Transcription Factors
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Identity

PubMed Central ID

  • PMC2757870

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20090738

PubMed ID

  • 19752183
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Additional Document Info

start page

  • 2151

end page

  • 2159

volume

  • 206

issue

  • 10

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