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The Year in Hematology pp 287–304Cite as

The Production of Immunoglobulins by Mouse Myeloma Cells

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Abstract

When a foreign substance is introduced into the body, the organism responds by synthesizing relatively large amounts of immunoglobulins which will react specifically with the immunogen. Originally, this was thought to involve a relatively straightforward series of events in which antigens were processed by phagocytic cells, plasma cell precursors representing selected clones were activated by specific antigens, and then cell proliferation and differentiation led to the production of specific antibodies. However, within this model it was not clear how recognition of self, tolerance, and the availability of precursor cells ready to make every possible antibody was achieved. Although these and other difficult questions have still not been resolved, it has become clear that between the initial introduction of antigen and the activation of the plasma cell to produce antibodies, the body carries out a highly complex series of events involving a multiplicity of signals mediated through soluble factors and the direct and indirect interactions of multiple cell types. Subpopulations of thymus (T) derived and bone marrow (or in the bird, bursa of Fabricius) (B) derived lymphocytes interact with macrophages and with each other to produce negative (suppressive) or positive (collaborative) responses. Genes are activated. Some cells are stimulated to replicate and differentiate whereas others are prevented from responding. All this requires what Jerne (1974) has called a “network of information” and is so complex that the details are only just beginning to be discussed.

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References

  • Abraham, K. A., Pryme, I. F., Abro, A., and Dowben, R. M., 1973, Polysomes in various phases of the cell cycle in synchronized plasmacytoma cells, Exp. Cell Res. 82:95.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, J., Coutinho, A., Melchers, F., and Watanabe, T., 1976, Growth and maturation of lymphocytes in culture, in “The Origins of Lymphocyte Diversity,” Cold Spring Harbor Symp. Quant. Biol. XLI (in press).

    Google Scholar 

  • Bailey, L. K., Hannestad, K., and Eisen, H. N., 1973, Aberrant immunoglobulin production in stable mouse myeloma tumor variants, Fed. Proc. 32:1013.

    Google Scholar 

  • Baumal, R., and Scharff, M. D., 1973, Synthesis, assembly and secretion of mouse immunoglobulin, Transplant. Rev. 14:163.

    PubMed  CAS  Google Scholar 

  • Baumal, R., and Scharff, M. D., 1976, Immunoglobulin biosynthesis by the MOPC 173 mouse myeloma tumor and variant spleen clones, J. Immunol. 116:65.

    PubMed  CAS  Google Scholar 

  • Baumal, R., Potter, M., and Scharff, M. D., 1971, Synthesis, assembly and secretion of gammaglobulin by mouse myeloma cells, J. Exp. Med. 134:1316.

    Article  PubMed  CAS  Google Scholar 

  • Baumal, R., Birshtein, B. K., Coffino, P., and Scharff, M. D., 1973, Mutations in immunoglobulin-producing mouse myeloma cells, Science 182:164.

    Article  PubMed  CAS  Google Scholar 

  • Bergsagel, D. E., Ogawa, M., and Librach, S. L., 1975, Mouse myeloma, Arch. Intern. Med. 135:109.

    Article  PubMed  CAS  Google Scholar 

  • Bernardini, A., and Tonegawa, S., 1974, Hybridization studies with an antibody heavy chain mRNA, FEBS Lett. 41:73.

    Article  PubMed  CAS  Google Scholar 

  • Birshtein, B. K., Preud’homme, J.-L., and Scharff, M. D., 1974, Variants of mouse myeloma cells that produce short immunoglobulin heavy chains, Proc. Nat. Acad. Sci. U.S.A. 71:3478.

    Article  CAS  Google Scholar 

  • Cebra, J. J., 1969, Immunoglobulins and immunocytes, Bacteriol. Rev. 33:159.

    PubMed  CAS  Google Scholar 

  • Coffino, P., and Scharff, M. D., 1971, Rate of somatic mutation in immunoglobulin production by mouse myeloma cells, Proc. Nat. Acad. Sci. U.S.A. 68:219.

    Article  CAS  Google Scholar 

  • Coffino, P., Knowles, B., Nathenson, S., and Scharff, M. D., 1971, Suppression of immunoglobulin synthesis by cellular hybridization, Nature New Biol. 231:87.

    PubMed  CAS  Google Scholar 

  • Coffino, P., Baumal, R., Laskov, R., and Scharff, M. D., 1972, Cloning of mouse myeloma cells and detection of rare variants, J. Cell. Physiol. 79:429.

    Article  PubMed  CAS  Google Scholar 

  • Cooper, M. D., Kearney, J. F., Lydyard, P. M., Grossi, C. E., and Lawton, A. R., 1976, Comparative analysis of B-cell generation in mouse, man and chicken, in “Origins of Lymphocyte Diversity,” Cold Spring Harbor Symp. Quant. Biol. XLI (in press).

    Google Scholar 

  • Cotton, R. G. H., Secher, D. S., and Milstein, C., 1973, Somatic mutation and the origin of antibody diversity. Clonal variability of the immunoglobulin produced by MOPC 21 cells in culture, Eur. J. Immunol. 3:135.

    Article  CAS  Google Scholar 

  • Cowan, N. J., Secher, D. S., and Milstein, C., 1974, Intracellular immunoglobulin chain synthesis in nonsecreting variants of a mouse myeloma: Detection of inactive light chain messenger RNA, J. Mol. Biol. 90:691.

    Article  PubMed  CAS  Google Scholar 

  • Davis, F. M., and Adelberg, E. A., 1973, Use of somatic cell hybrids for analysis of the differentiated state, Bacteriol. Rev. 37:197.

    PubMed  CAS  Google Scholar 

  • Franklin, E. C., and Frangione, B., 1975, Structural variants of human and murine immunoglobulins, in Contemporary Topics in Molecular Immunology, Vol. 4 (F. P. Inman and W. J. Mandy, eds.), Plenum Press, New York.

    Google Scholar 

  • Green, M., Graves, P. N., Zehavi-Willner, T., Mclnnes, J., and Pestka, S., 1975, Cell-free translation of immunoglobulin messenger RNA from MOPC 315 plasmacytoma and MOPC 315 NR, a variant synthesizing only light chain, Proc. Nat. Acad. Sci. U.S.A. 72:224.

    Article  CAS  Google Scholar 

  • Harrison, T. M., Brownlee, G. G., and Milstein, C., 1974, Studies on polysomemembrane interactions in mouse myeloma cells, Eur. J. Biochem. 47:613.

    Article  PubMed  CAS  Google Scholar 

  • Hobbs, J. R., 1971, Immunocytoma o’mice an’ men, Br. Med. J. 2:67.

    Article  PubMed  CAS  Google Scholar 

  • Hollander, V. P., Takakura, K., and Yamada, H., 1968, Endocrine factors in the pathogenesis of plasma cell tumors, Recent Prog. Horm. Res. 24:81.

    PubMed  CAS  Google Scholar 

  • Hood, L., Campbell, J. H., and Elgin, S. C. R., 1975, The organization, expression, and evolution of antibody genes and other multigene families, Annu. Rev. Genet. 9:305.

    Article  PubMed  CAS  Google Scholar 

  • Horibata, K., and Harris, A. W., 1970, Mouse myelomas and lymphomas in culture, Exp. Cell Res. 60:61.

    Article  PubMed  CAS  Google Scholar 

  • Jerne, N. K., 1974, Towards a network theory of the immune system, Ann. Immunol. (Inst. Pasteur) 125C:373.

    CAS  Google Scholar 

  • Kohler, G., and Milstein, C., 1975, Continuous cultures of fused cells secreting antibody of predefined specificity, Nature (London) 256:495.

    Article  CAS  Google Scholar 

  • Kuehl, W. M., Kaplan, B. A., Scharff, M. D., Nav, M., Honjo, T., and Leder, P., 1975, Characterization of light chain and light chain constant region fragment mRNAs in MPC 11 mouse myeloma cells and variants, Cell 5:139.

    Article  PubMed  CAS  Google Scholar 

  • Lam, C., and Stevenson, G., 1973, Detection in normal plasma of immunoglobulin resembling the protein of y-chain disease, Nature (London) 246:419.

    Article  CAS  Google Scholar 

  • Laskov, R., and Scharff, M. D., 1970, Synthesis, assembly, and secretion of gammaglobulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor 11 to culture, cloning and characterization of gammaglobulin synthesis, J. Exp. Med. 131:515.

    Article  PubMed  CAS  Google Scholar 

  • Leder, P., Honjo, T., Packman, S., Swan, D., Nav, M., and Norman, B., 1975, The organization and diversity of immunoglobulin K and y genes, in Molecular Approaches to Immunology (E. E. Smith and D. S. Ribbons, eds.), p. 173, Academic Press, New York.

    Chapter  Google Scholar 

  • Liberti, P., and Baglioni, C., 1973, Synthesis of immunoglobulin and nuclear protein in synchronized mouse myeloma cells, J. Cell. Physiol. 82:113.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, R., Mantel, N., and Humphrey, W. Jr., 1961, Ascites production in 17 mice strains, Proc. Soc. Exp. Biol. Med. 107:163.

    Article  PubMed  CAS  Google Scholar 

  • Lisowska-Bernstein, B., Lamm, M. E., and Vassali, P., 1970, Synthesis of immunoglobulin heavy and light chains by the free ribosomes of a mouse plasma cell tumor, Proc. Nat. Acad. Sci. U.S.A. 66:425.

    Article  CAS  Google Scholar 

  • Lyons, R. M., Chaplin, H., and Tillack, T. W., 1975, Gamma-heavy chain disease: Rapid sustained response to cyclophosphamide and prednisone, Blood 46:1.

    PubMed  CAS  Google Scholar 

  • Margulies, D. H., Kuehl, W. M., and Scharff, M. D., 1976, Somatic cell hybridization of mouse myeloma cells, Cell 8:405.

    Article  PubMed  CAS  Google Scholar 

  • Margulies, D. H., Cieplinski, W., Dharmgrongartama, B., Gefter, M. L., Morrison, S. L., Kelley, T., and Scharff, M. D., 1976b, Regulation of immunoglobulin expression in mouse myeloma cells, in “Origins of Lymphocyte Diversity,” Cold Spring Harbor Symp. Quant. Biol. XLI (in press).

    Google Scholar 

  • McKean, D. J., Potter, M., and Hood, L., 1972, Amino acid sequence comparison of three new Balb/C mouse kappa chains, Fed. Proc. 31:772 (Abstract).

    Google Scholar 

  • Melchers, F., 1971, The secretion of a Bence-Jones type light chain from a mouse plasmacytoma, Eur. J. Immunol. 1:330.

    Article  PubMed  CAS  Google Scholar 

  • Melchers, F., and Knopf, P. M., 1967, Biosynthesis of the carbohydrate portion of immunoglobulin chains: Possible relation to secretions, in “Antibodies,” Cold Spring Harbor Symp. Quant Biol, p. 255.

    Google Scholar 

  • Merwin, R. M., and Algire, G. H., 1959, Induction of plasma cell neoplasms and fibrosarcomas in BALB/c mice carrying diffusion chambers, Proc. Soc. Exp. Biol. Med. 101:437.

    Article  PubMed  CAS  Google Scholar 

  • Merwin, R. M., and Redman, L. W., 1963, Induction of plasma cell tumors and sarcomas in mice by diffusion chambers placed in the peritoneal cavity, J. Nat. Cancer Inst. 31:998.

    Google Scholar 

  • Milstein, C., Adetugbo, K., Brownlee, G. G., Cowan, N. J., Proudfoot, N. J., Rabbitts, T. H., and Secher, D. S., 1975, Immunoglobulin genes in a mouse myeloma and in mutant clones, in Molecular Approaches to Immunology (E. E. Smith and D. W. Ribbons, eds.), p. 131, Academic Press, New York.

    Chapter  Google Scholar 

  • Morrison, S. L., and Scharff, M. D., 1975, Heavy chain-producing variants of a mouse myeloma cell line, J. Immunol. 114:655.

    PubMed  CAS  Google Scholar 

  • Mushinski, J. F., 1971, γA half molecules: Defective heavy chain mutants in mouse myeloma proteins, J. Immunol. 106:41.

    PubMed  CAS  Google Scholar 

  • Osserman, E. F., and Takatsuki, K., 1964, Considerations regarding the pathogenesis of the plasmacytic dyserasias, Scand. J. Haematol. 4 (Suppl.):28.

    Google Scholar 

  • Periman, P., 1970, IgG synthesis in hybrid cells from an antibody-producing mouse myeloma and an L cell substrain, Nature (London) 228:1086.

    Article  CAS  Google Scholar 

  • Preud’homme, J.-L., Buxbam, J., and Scharff, M. D., 1973, Mutagenesis of mouse myeloma cells with “Melphalan,” Nature (London) 245:320.

    Article  CAS  Google Scholar 

  • Preud’homme, J.-L., Birshtein, B. K., and Scharff, M. D., 1975, Variants of mouse myeloma cells that produce short immunoglobulin heavy chains, Proc. Nat. Acad. Sci. U.S.A. 72:1427.

    Article  CAS  Google Scholar 

  • Pottengill, G. S., and Sorensen, G. D., 1967, Murine myeloma cells in suspension culture, Exp. Cell Res. 47:608.

    Article  Google Scholar 

  • [Potter, M., 1967, The plasma cell tumors and myeloma proteins of mice, in Methods in Cancer Research (H. Busch, ed.), Vol. II, p. 105, Academic Press, New York.

    Google Scholar 

  • Potter, M., 1972, Immunoglobulin-producing tumors and myeloma proteins of mice, Physiol. Rev. 52:631.

    PubMed  CAS  Google Scholar 

  • Potter, M., and Boyce, C., 1962, Induction of plasma cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants, Nature (London) 193:1086.

    Article  CAS  Google Scholar 

  • Potter, M., and Kuff, E. L., 1964, Disorders in the differentiation of protein secretion in neoplastic plasma cells, J. Mol. Biol. 9:537.

    Article  PubMed  CAS  Google Scholar 

  • Potter, M., Sklar, M. D., and Rowe, W. P., 1973, Rapid viral induction of plasmacytomas in pristane-primed BALB/c mice, Science 182:592.

    Article  PubMed  CAS  Google Scholar 

  • Pryme, I. F., Garantun-Tjeldsto, O., Birekbichler, P. J., Weltman, J. K., and Dowben, R. M., 1973, Synthesis of immunoglobulins by membrane-bound polysomes and free polysomes from plasmacytoma cells, Eur. J. Biochem. 33:374.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, E. A., Smith, D. F., and Appella, E., 1974, Chemical characterization of a mouse immunoglobulin A heavy chain with a 100 residue deletion, J. Biol. Chem. 249:6605.

    PubMed  CAS  Google Scholar 

  • Rothman, S. S., 1975, Protein transport by the pancreas, Science 190:747.

    Article  PubMed  CAS  Google Scholar 

  • Scharff, M. D., and Laskov, R., 1970, Synthesis and assembly of immunoglobulin polypeptide chains, Prog. Allergy 14:37.

    PubMed  CAS  Google Scholar 

  • Scharff, M. D., Birshtein, B. K., Dharmgrongartama, B., Frank, L., Kelly, T., Kuehl, W. M., Margulies, D. H., Morrison, S. L., Preud’homme, J.-L., and Weitzman, S., 1975, The use of mutant myeloma cells to explore the production of immunoglobulins, in Molecular Approaches to Immunology (E. E. Smith and D. M. Ribbons, eds.), p. 109, Academic Press, New York.

    Chapter  Google Scholar 

  • Scheele, G. A., Dobberstein, B., Devillers-Thiery, A., and Blobel, G., 1975, In vitro translation of cell fractions from dog pancreas, J. Cell Biol. 67:385a.

    Google Scholar 

  • Takakura, K., Yamada, H., Weber, A. H., and Hollander, V. P., 1967, Studies on the pathogenesis of plasma cell tumors, effect of sex hormones on the development of plasma cell tumors, Cancer Res. 27:932.

    PubMed  CAS  Google Scholar 

  • Tonegawa, S., Hozumi, N., Matthyssens, G., and Schuller, R., 1976, Somatic changes in content and context of immunoglobulin genes, in “Origin of Lymphocyte Diversity,” Cold Spring Harbor Symp. Quant. Biol. XLI (in press).

    Google Scholar 

  • Weigert, M., Cesari, M., Yonkovich, S. J., and Cohn, M., 1970, Variability in the lambda light chain sequences of mouse antibody, Nature (London) 228:1045.

    Article  CAS  Google Scholar 

  • Weitzman, S., and Scharff, M. D., 1976, Mouse myeloma mutants blocked in the assembly, glycosylation, and secretion of immunoglobulin, J. Mol. Biol. 102:237.

    Article  PubMed  CAS  Google Scholar 

  • Williamson, A. R., 1976, The biological origin of antibody diversity, Annu. Rev. Biochem. 45:467.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA

    W. Cieplinski & M. D. Scharff

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  1. W. Cieplinski
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  2. M. D. Scharff
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Editors and Affiliations

  1. Graduate School of Arts and Science, New York University, New York, New York, USA

    Albert S. Gordon Ph.D., F.R.S.M.  & Joseph LoBue Ph.D.  & 

  2. New York University School of Medicine, New York, New York, USA

    Robert Silber M.D.

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Cieplinski, W., Scharff, M.D. (1977). The Production of Immunoglobulins by Mouse Myeloma Cells. In: Gordon, A.S., Silber, R., LoBue, J. (eds) The Year in Hematology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-6688-9_10

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  • DOI: https://doi.org/10.1007/978-1-4899-6688-9_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-6690-2

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