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

Journal Article

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. © 2013 Macmillan Publishers Limited All rights reserved.

Full Text

Duke Authors

Cited Authors

  • Dilillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF

Published Date

  • 2013

Published In

Volume / Issue

  • 27 / 1

Start / End Page

  • 170 - 182

International Standard Serial Number (ISSN)

  • 0887-6924

Digital Object Identifier (DOI)

  • 10.1038/leu.2012.165