Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture.
We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.
Bock
G H
GH
Metabolism Branch, DCBDC, National Cancer Institute, N.I.H., Bethesda, MD.
Long
C A
CA
Riley
M L
ML
White
J D
JD
Kurman
C C
CC
Fleisher
T A
TA
Tsokos
M
M
Brown
M
M
Serbousek
D
D
Schwietermann
W D
WD
D000328:Adult; D002999:Clone Cells; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007136:Immunoglobulins; D015850:Interleukin-6; D012333:RNA, Messenger