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Immunology

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function

Leukemia volume 27, pages 170–182 (2013)Cite this article

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Abstract

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5+ CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgVH mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.

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Acknowledgements

We thank Dr Barbara Goodman for CLL cytogenetic analyses, Dr Jonathan Poe for suggestions and data analysis and Robert Streilein for patient’s cell preparations. These studies were supported by grants from the NIH (AI56363 and Southeastern Regional Center of Excellence for Emerging Infections and Biodefense (U54 AI057157)), the Lymphoma Research Foundation (to TFT), the Leukemia and Lymphoma Society and VA Research Service (to JBW), and the Associazione Italiana per la Ricerca sul Cancro (to GR).

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Authors and Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, NC, USA

    D J DiLillo, A Yoshizaki, M Horikawa, J M Bryant, Y Iwata, T Matsushita, G M Venturi & T F Tedder

  2. Department of Medicine, Division of Hematology, Duke University Medical and Durham VA Medical Centers, Durham, NC, USA

    J B Weinberg, K M Matta, Y Chen & A D Volkheimer

  3. Molecular Oncology Laboratory, Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy

    G Russo

  4. Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA

    J P Gockerman, J O Moore, L F Diehl, D R Friedman & M C Lanasa

  5. Department of Dermatology, Duke University Medical and Durham VA Medical Centers, Durham, NC, USA

    R P Hall

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  1. D J DiLillo
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Correspondence to T F Tedder.

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TFT is a consultant and shareholder for Angelica Therapeutics Inc. The remaining authors declare no conflict of interest.

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DiLillo, D., Weinberg, J., Yoshizaki, A. et al. Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function. Leukemia 27, 170–182 (2013). https://doi.org/10.1038/leu.2012.165

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