Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function.
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.
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
D J
DJ
DiLillo
J B
JB
Weinberg
A
A
Yoshizaki
M
M
Horikawa
J M
JM
Bryant
Y
Y
Iwata
T
T
Matsushita
K M
KM
Matta
Y
Y
Chen
G M
GM
Venturi
G
G
Russo
J P
JP
Gockerman
J O
JO
Moore
L F
LF
Diehl
A D
AD
Volkheimer
D R
DR
Friedman
M C
MC
Lanasa
R P
RP
Hall
T F
TF
Tedder
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology*
D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse; D016753:Interleukin-10