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Plasma cell differentiation requires the transcription factor XBP-1

Author

Listed:
  • Andreas M. Reimold

    (Harvard School of Public Health
    Harvard Medical School
    University of Texas Southwestern Medical Center at Dallas)

  • Neal N. Iwakoshi

    (Harvard School of Public Health)

  • John Manis

    (Howard Hughes Medical Institute, Children's Hospital)

  • Prashanth Vallabhajosyula

    (Harvard School of Public Health)

  • Eva Szomolanyi-Tsuda

    (University of Massachusetts Medical School)

  • Ellen M. Gravallese

    (Beth Israel Deaconess Medical Center)

  • Daniel Friend

    (Harvard Medical School)

  • Michael J. Grusby

    (Harvard School of Public Health
    Harvard Medical School)

  • Frederick Alt

    (Howard Hughes Medical Institute, Children's Hospital)

  • Laurie H. Glimcher

    (Harvard School of Public Health
    Harvard Medical School)

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.

Suggested Citation

  • Andreas M. Reimold & Neal N. Iwakoshi & John Manis & Prashanth Vallabhajosyula & Eva Szomolanyi-Tsuda & Ellen M. Gravallese & Daniel Friend & Michael J. Grusby & Frederick Alt & Laurie H. Glimcher, 2001. "Plasma cell differentiation requires the transcription factor XBP-1," Nature, Nature, vol. 412(6844), pages 300-307, July.
    • Handle: RePEc:nat:nature:v:412:y:2001:i:6844:d:10.1038_35085509
    DOI: 10.1038/35085509
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    Cited by:

    1. Vladimir Potapov & Jenifer B Kaplan & Amy E Keating, 2015. "Data-Driven Prediction and Design of bZIP Coiled-Coil Interactions," PLOS Computational Biology, Public Library of Science, vol. 11(2), pages 1-28, February.
    2. Jianfeng Wu & Kang Yang & Shaowei Cai & Xiaohan Zhang & Lichen Hu & Fanjia Lin & Su-qin Wu & Changchun Xiao & Wen-Hsien Liu & Jiahuai Han, 2022. "A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Ki Oh & Yun Jae Yoo & Luke A. Torre-Healy & Manisha Rao & Danielle Fassler & Pei Wang & Michael Caponegro & Mei Gao & Joseph Kim & Aaron Sasson & Georgios Georgakis & Scott Powers & Richard A. Moffitt, 2023. "Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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