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Rapid Death of Follicular B Cells and Burkitt Lymphoma Cells Effectuated by Xbp1s

Yi-Ting Chen and John T. Kung
J Immunol May 6, 2020, ji2000172; DOI: https://doi.org/10.4049/jimmunol.2000172
Yi-Ting Chen
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan
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John T. Kung
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan
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Key Points

  • Xbp1s inhibits BCR tonic signaling, causing rapid death of FOB cells but not MZB cells.

  • Among many UPR-activated molecules, Xbp1s is the only one that causes FOB cell death.

  • BCR-mediated survival and clonal expansion responses are independently regulated.

Abstract

BCR-mediated tonic signaling is an indispensable requirement for the survival of follicular B (FOB) cells and Burkitt lymphoma (BL) cells. FOB cells of the I-A12% mutant mouse express unfolded protein response and are extremely short lived. Among the myriad molecules activated by unfolded protein response in I-A12% B cells, Xbp1s singularly “hijacked” p110 from p85:p110 heterodimeric PI3K, thereby abating BCR tonic signaling, resulting in their extremely short lifespan. Long-lived normal FOB cells became short lived upon ectopic Xbp1s expression. The proapoptotic Xbp1s role in FOB cells starkly contrasts with its antithetical prosurvival function in plasma cells. Also, tonic signaling and clonal expansion, two important functions mediated by the same BCR, operate in independent and distinct manners. Furthermore, concerning the development of new therapeutic treatment of drug-refractory BL patients, our finding of Xbp1s-mediated rapid death of BL cells brings forth a conceptual advancement based on blocking PI3K heterodimer formation rather than inhibition of PI3K enzyme activity.

Footnotes

  • This work was supported by the National Science Council (Grants NSC96-3112-B-001-007 and NSC96-3112-B-001-008), the Ministry of Science and Technology (Grants 105-2320-B-001-007, 107-2320-B-001-002, and 108-2320-B-001-026), and the Academia Sinica (Grants AS-91-IMB1PP and AS-95-TP-B06).

  • Received February 13, 2020.
  • Accepted April 17, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.

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The Journal of Immunology: 206 (3)
The Journal of Immunology
Vol. 206, Issue 3
1 Feb 2021
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Rapid Death of Follicular B Cells and Burkitt Lymphoma Cells Effectuated by Xbp1s
Yi-Ting Chen, John T. Kung
The Journal of Immunology May 6, 2020, ji2000172; DOI: 10.4049/jimmunol.2000172

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Rapid Death of Follicular B Cells and Burkitt Lymphoma Cells Effectuated by Xbp1s
Yi-Ting Chen, John T. Kung
The Journal of Immunology May 6, 2020, ji2000172; DOI: 10.4049/jimmunol.2000172
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Print ISSN 0022-1767        Online ISSN 1550-6606