A novel mature B-cell line (DOBIL-6) producing both parathyroid hormone-related protein and interleukin-6 from a myeloma patient presenting with hypercalcaemia.
A novel human EBV-negative B-cell line, designated DOBIL-6, was established from a patient with non-secretary myeloma. The DOBIL-6 cell has cytoplasmic gamma protein and expresses CD19, 20, 38, 45RO, VLA-4 and PCA-1 antigens, but lacks CD10, 45RA and VLA5 antigens. Chromosome analysis showed that DOBIL-6 cells had many complex structural abnormalities, including t(11;4) (q13;q32), which were consistent with that of the fresh tumour cells. Interestingly, abundant interleukin-6 (IL-6) and parathyroid hormone-related protein (PTHrP) accumulated in the culture supernatant of DOBIL-6 cells. Hypercalcaemia and splenomegaly associated with plasma cell proliferations which resulted in the expansion of the light zones in the follicles were observed in DOBIL-6 transplanted nude mice. RT-PCR analysis detected mRNA for PTHrP, and IL-6 as well as its receptor (GP80) in DOBIL-6 cells. Treatment of the DOBIL-6 cells with neutralizing anti-IL-6 antibody inhibited their growth in a dose-dependent manner, whereas the addition of exogenous IL-6 stimulated it in serum-depleted conditions. These findings suggest that both IL-6 and PTHrP are produced in DOBIL-6 cells, and that IL-6 promotes its growth by an autocrine mechanism. Since IL-6 is known to stimulate not only the growth of B-cell neoplasms but also osteoclastic bone resorption by cooperating with PTHrP, this simultaneous production of IL-6 and PTHrP might be synergistically linked and play a role in the development of hypercalcaemia of the patient. The DOBIL-6 cell is a useful tool to clarify the mechanism of hypercalcaemia associated with mature B-cell neoplasms.
First Department of Internal Medicine, Kagawa Medical University, Japan.
M
M
Ohmori
M
M
Nagai
M
M
Fujita
H
H
Dobashi
T
T
Tasaka
G
G
Yamaoka
K
K
Kawanishi
M
M
Taniwaki
J
J
Takahara
D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007621:Karyotyping; D009101:Multiple Myeloma / Q000150:complications / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism
D015850:Interleukin-6; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins