Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line.
A new human monoclonal plasma cell line, designated UTMC-2, was established from the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related multiple myeloma. The cultured cells were Epstein-Barr virus-negative and exhibited the morphological and ultrastructural features characteristic of plasma cells. Immunohistochemical analyses revealed the presence of cytoplasmic IgA kappa as well as the plasma cell-associated surface antigens CD38 and CD56. Other B-cell markers, including CD10, CD19, CD20, and HLA-DR, were absent. The UTMC-2 cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA kappa synthesis and cell proliferation in a dose-dependent manner. In contrast, an IL-6 antisense oligonucleotide had an opposite effect. Although the UTMC-2 cells expressed IL-6 mRNA (as demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine in cell culture supernatants was less than that detectable by the enzyme-linked immunosorbent assay (ELISA) employed (i.e. <3 pg/ml). Further, cell growth was not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric analysis revealed that IL-6 receptors present on the surface of the UTMC-2 cells were not saturated with endogenous IL-6. Taken together, these results indicate that, in this human plasma cell line, IL-6 functions uniquely in an intracellular autocrine fashion to enhance Ig synthesis and cell growth. In this respect, the UTMC-2 cells represent a novel resource for further study of the role of IL-6 in the pathogenesis of multiple myeloma.
Ozaki
S
S
Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.
Wolfenbarger
D
D
deBram-Hart
M
M
Kanangat
S
S
Weiss
D T
DT
Solomon
A
A
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019002:CD56 Antigen; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008562:Membrane Glycoproteins; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007070:Immunoglobulin A; D007145:Immunoglobulin kappa-Chains; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1