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

D. J. Dilillo, J. B. Weinberg, A. Yoshizaki, M. Horikawa, J. M. Bryant, Y. Iwata, T. Matsushita, K. M. Matta, Y. Chen, G. M. Venturi, G. Russo, J. P. Gockerman, J. O. Moore, L. F. Diehl, A. D. Volkheimer, D. R. Friedman, M. C. Lanasa, R. P. Hall, T. F. Tedder

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

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 IgV H 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.

Original languageEnglish
Pages (from-to)170-182
Number of pages13
JournalLeukemia
Volume27
Issue number1
DOIs
Publication statusPublished - 01-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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