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Plasma cell differentiation requires the transcription factor XBP-1

Nature volume 412, pages 300–307 (2001)Cite this article

Abstract

Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells.

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Figure 1: XBP-1 expression in rheumatoid synovium.
Figure 2: Induction of XBP-1 is upstream and downstream of signals that drive plasma-cell differentiation.
Figure 3: Gene targeting to generate XBP-1-deficient cells.
Figure 4: XBP-1 is required for immunoglobulin secretion.
Figure 5
Figure 6: In vitro phenotype of XBP-1-/- B cells.
Figure 7: Decreased formation of plasma cells in the absence of XBP-1.
Figure 8: XBP-1-/- lymphocytes do not respond to T-cell-independent or -dependent antigens or to polyoma virus in vivo.

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Acknowledgements

This work was supported by grants from the National Institutes of Health (L.H.G., F.A. and A.R.) and the Hood Foundation (J.M.), and a gift from the G. Harold and Leila Y. Mathers Charitable Foundation (L.H.G.). We thank A. Erlebacher, K. Mowen and S. Peng for a review of the manuscript; L. Davidson and K. Sigrist for production of XBP/RAG-/- chimaeras; M. Wheaton for technical assistance with the polyoma virus experiments; C. McCall for preparation of the manuscript; and A. Bottaro and I. Kuzin for IgM primers.

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Author notes

  1. Andreas M. Reimold

    Present address: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Texas, 75390, USA

  2. Andreas M. Reimold, Neal N. Iwakoshi and Ellen M. Gravallese: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology and Infectious Diseases, Harvard School of Public Health,

    Andreas M. Reimold, Neal N. Iwakoshi, Prashanth Vallabhajosyula, Michael J. Grusby & Laurie H. Glimcher

  2. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Andreas M. Reimold, Daniel Friend, Michael J. Grusby & Laurie H. Glimcher

  3. Howard Hughes Medical Institute, Children's Hospital, Boston, 02115, Massachusetts, USA

    John Manis & Frederick Alt

  4. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, 02115, Massachusetts, USA

    Ellen M. Gravallese

  5. Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, Massachusetts, USA

    Eva Szomolanyi-Tsuda

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Reimold, A., Iwakoshi, N., Manis, J. et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature 412, 300–307 (2001). https://doi.org/10.1038/35085509

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