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Molecular targets for therapy

The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

Leukemia volume 30, pages 163–172 (2016)Cite this article

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Abstract

Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory elements with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B-cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is critical for B-cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing regulatory B cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor transmembrane activator and cyclophilin ligand interactor. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL.

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Acknowledgements

We thank Professor Stephen Jane for critical appraisal of the manuscript, the AMREP flow cytometry team for technical assistance, the AMREP Animal Service staff for colony health management and the ALLG Tissue Bank for provision of PBL samples. We especially thank all patients involved in this study. SBT is supported by an NHMRC RD Wright Career Development Fellowship. This study was funded by the Worldwide Cancer Research (formerly Association for International Cancer Research (AICR)) UK and the National Health and Medical Research Council (NHMRC) of Australia.

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Authors and Affiliations

  1. Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia

    D Saulep-Easton, F B Vincent, P S Quah & F Mackay

  2. Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia

    A Wei & S B Ting

  3. Division of Blood Cancers, Department of Medicine, Australian Centre for Blood Diseases, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia

    A Wei & S B Ting

  4. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA

    C M Croce

  5. Department of Haematology, Peter MacCallum Cancer Centre, St. Andrews’s Place, East Melbourne, Victoria, Australia

    C Tam

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Saulep-Easton, D., Vincent, F., Quah, P. et al. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells. Leukemia 30, 163–172 (2016). https://doi.org/10.1038/leu.2015.174

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