A NOVEL MATURE B-CELL LINE (DOBIL-6) PRODUCING BOTH PARATHYROID HORMONE-RELATED PROTEIN AND INTERLEUKIN-6 FROM A MYELOMA PATIENT PRESENTINGWITH HYPERCALCEMIA

A novel human EBV-negative B-cell line, designated DOBIL-6, was establ ished from a patient with nonsecretary myeloma. The DOBIL-6 cell has c ytoplasmic gamma protein and expresses CD19, 20, 38, 45RO, VLA-4 and P CA-1 antigens, but lacks CD10, 45RA and VLA5 antigens. Chromosome anal ysis showed that DOBIL-6 cells had many complex structural abnormaliti es, including t(11;14) (q13;q32), which were consistent with that of t he fresh tumour cells. Interestingly, abundant interleukin-6 (IL-6) an d parathyroid hormone-related protein (PTHrP) accumulated in the cultu re supernatant of DOBIL-6 cells. Hypercalcaemia and splenomegaly assoc iated with plasma cell proliferations which resulted in the expansion of the light zones in the follicles were observed in DOBIL-6 transplan ted nude mice. RT-PCR analysis detected mRNA for PTHrP, and IL-6 as we ll as its receptor (GP80) in DOBIL-6 cells. Treatment of the DOBIL-6 c ells with neutralizing anti-IL-6 antibody inhibited their growth in a dose-dependent manner, whereas the addition of exogenous IL-6 stimulat ed it in serum-depleted conditions. These findings suggest that both I L-6 and PTHrP are produced in DOBIL-6 cells, and that IL-6 promotes it s growth by an autocrine mechanism. Since IL-6 is known to stimulate n ot only the growth of B-cell neoplasms but also osteoclastic bone reso rption by cooperating with PTHrP, this simultaneous production of IL-6 and PTHrP might be synergistically linked and play a role in the deve lopment of hypercalcaemia of the patient. The DOBIL-6 cell is a useful tool to clarify the mechanism of hypercalcaemia associated with matur e B-cell neoplasms.