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Synthesis of Immunoglobulins by Human Cell Lines in Tissue Culture

From the Immunology Branch, National Cancer Institute, National Institutes of Health, United States Public Health Service, Department of Health, Education, and Welfare, Bethesda, Maryland

Abstract

Immunoglobulin synthesis has been demonstrated in 19 of 27 lymphoid cell lines in continuous culture derived from patients with a variety of malignant disorders. Soluble proteins derived from cells grown in media containing C¹⁴-amino acids were tested by radioimmunoelectrophoresis with antiserums specific for IgG, IgA, IgM and IgD and and light polypeptide chains. Immunoglobulins synthesized in vitro ranged from only one light chain type to two heavy chains and two light chain types in individual culture lines.

Physical and immunochemical techniques showed that many of the newly synthesized heavy and light chains were linked to form 7 S or 18 S immunoglobulin molecules. Immunochemical tests indicated that immunogloblins produced by the cultured cell lines were very similar or identical to normal human immunoglobulins. Stability of immunoglobulin formation was assessed by repeat tests of 15 cell lines, and only two cell lines varied in results. The immunoglobulins produced by these cells are electrophoretically homogeneous and thus bear some resemblance to myeloma proteins.

Investigation of serum from patients with Burkitt's lymphoma and chronic myelogenous leukemia, failed to reveal serum immunoglobulin components comparable to the proteins identified in culture. These findings indicate that lymphoid cells producing immunoglobulin in culture may be functionally different from the predominant malignant cell (in vivo) in the donor patients and from the malignant plasma cells of patients with multiple myeloma. It seems possible that the lymphoid cells in culture are derived from a minor part of the malignant cell population or from normal cells.

Herpes-like virus particles are present in most of the cell lines. Immunoglobulin production appeared to be independent of the presence of viral particles.