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Published on: May 10, 2017
Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line
S Ozaki1, D Wolfenbarger, M deBram-Hart
1Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.
Insights
A new human plasma cell line, UTMC-2, shows interleukin-6 (IL-6) acts intracellularly to boost immunoglobulin (Ig) production and growth. This discovery offers a novel model for studying multiple myeloma pathogenesis.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Multiple myeloma is a cancer of plasma cells.
- Interleukin-6 (IL-6) is a key cytokine implicated in multiple myeloma pathogenesis.
- Understanding the precise mechanisms of IL-6 action is crucial for developing targeted therapies.
Purpose of the Study:
- To establish and characterize a new human monoclonal plasma cell line, UTMC-2.
- To investigate the role and mechanism of IL-6 action in this novel cell line.
- To explore the potential of UTMC-2 as a model for multiple myeloma research.
Main Methods:
- Establishment of a human plasma cell line (UTMC-2) from patient pleural effusion.
- Immunohistochemistry and flow cytometry for cell surface and cytoplasmic marker analysis.
- Reverse transcriptase-polymerase chain reaction (RT-PCR) and ELISA for cytokine detection.
- Cell proliferation and Ig synthesis assays in response to IL-6 and IL-6 antisense oligonucleotides.
Main Results:
- UTMC-2 cells exhibited plasma cell morphology and expressed IgA kappa, CD38, and CD56, lacking other B-cell markers.
- IL-6 stimulation dose-dependently increased IgA kappa synthesis and cell proliferation.
- IL-6 mRNA and intracellular IL-6 were detected, but supernatant levels were very low (<3 pg/ml).
- IL-6 receptors were not saturated, and anti-IL-6 antibodies did not inhibit growth, suggesting intracellular action.
Conclusions:
- The UTMC-2 cell line demonstrates a unique intracellular autocrine mechanism of IL-6 action.
- IL-6 enhances Ig synthesis and cell growth via an intracellular pathway in this myeloma model.
- UTMC-2 provides a valuable resource for studying IL-6's role in multiple myeloma pathogenesis.
Abstract:
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.
