Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function.
Published
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.
Full Text
Duke Authors
- Diehl, Louis Frederic
- Friedman, Daphne Ruth
- Gockerman, Jon Paul
- Hall III, Russell P.
- Moore, Joseph Odell
- Tedder, Thomas Fletcher
- Weinberg, Joe Brice
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
- January 2013
Published In
Volume / Issue
- 27 / 1
Start / End Page
- 170 - 182
PubMed ID
- 22713648
Pubmed Central ID
- 22713648
Electronic International Standard Serial Number (EISSN)
- 1476-5551
Digital Object Identifier (DOI)
- 10.1038/leu.2012.165
Language
- eng
Conference Location
- England