Abstract
Murine B lymphoma cultured cell lines bearing membrane IgM and lacking the ability to secrete measurable amounts of IgM were fused with drug-resistant cell lines derived from the IgG2b-producing MPC-11 myeloma. Many of the hybrid clones synthesized and secreted large amounts of IgM, as judged by radial and double immunodiffusion in agar of culture supernatants and by polyacrylamide gel electrophoresis of biosynthetically labeled IgM. When fused with an IgG2b-producing myeloma, many of the hybrids also produced IgG2b, indicating that there was no suppression of the parental IgG synthesis in the hybrids. The amount of IgM or IgG2b secreted by the hybrids was higher than that secreted by myeloma cell lines. The synthesis of the gamma2b heavy chain of the MPC-11 myeloma was not reexpressed by fusion of a gamma2b nonproducer myeloma cell variant with B lymphoma. No other classes of Ig heavy chains, besides the gamma2b and the mu chains, were found to be secreted by any of more than 100 B lymphoma--myeloma hybrids examined. The results of the present work suggest that myeloma cells may fuse not only with normal plasma cells but also with less-mature normal B lymphocytes and that this fusion "induces" the maturation of B lymphocytes into IgM-secreting cells.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bergman Y., Haimovich J. Characterization of a carcinogen-induced murine B lymphocyte cell line of C3H/eB origin. Eur J Immunol. 1977 Jul;7(7):413–417. doi: 10.1002/eji.1830070702. [DOI] [PubMed] [Google Scholar]
- Bretscher P., Cohn M. A theory of self-nonself discrimination. Science. 1970 Sep 11;169(3950):1042–1049. doi: 10.1126/science.169.3950.1042. [DOI] [PubMed] [Google Scholar]
- Davis F. M., Adelberg E. A. Use of somatic cell hybrids for analysis of the differentiated state. Bacteriol Rev. 1973 Jun;37(2):197–214. doi: 10.1128/br.37.2.197-214.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dev V. G., Miller D. A., Allderdice P. W., Miller O. J. Method for locating the centromeres of mouse meiotic chromosomes and its application to T163H and T70H translocations. Exp Cell Res. 1972 Jul;73(1):259–262. doi: 10.1016/0014-4827(72)90132-2. [DOI] [PubMed] [Google Scholar]
- Fleming H., Haselkorn R. The program of protein synthesis during heterocyst differentiation in nitrogen-fixing blue-green algae. Cell. 1974 Oct;3(2):169–170. doi: 10.1016/0092-8674(74)90121-4. [DOI] [PubMed] [Google Scholar]
- Gearhart P. J., Sigal N. H., Klinman N. R. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. Proc Natl Acad Sci U S A. 1975 May;72(5):1707–1711. doi: 10.1073/pnas.72.5.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kishimoto T., Hirano T., Kuritani T., Yamamura Y., Ralph P., Good R. A. Induction of IgG production in human B lymphoblastoid cell lines with normal human T cells. Nature. 1978 Feb 23;271(5647):756–758. doi: 10.1038/271756a0. [DOI] [PubMed] [Google Scholar]
- Köhler G., Howe S. C., Milstein C. Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur J Immunol. 1976 Apr;6(4):292–295. doi: 10.1002/eji.1830060411. [DOI] [PubMed] [Google Scholar]
- Köhler G., Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976 Jul;6(7):511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
- Laskov R., Kimm K. J., Asofsky R. Induction of IgM secretion by fusing murine B-lymphoma with myeloma cells. Curr Top Microbiol Immunol. 1978;81:173–175. doi: 10.1007/978-3-642-67448-8_28. [DOI] [PubMed] [Google Scholar]
- Laskov R., Scharff M. D. Synthesis, assembly, and secretion of gamma globulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor-11 to culture, cloning, and characterization of gamma globulin subunits. J Exp Med. 1970 Mar 1;131(3):515–541. doi: 10.1084/jem.131.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levy R., Dilley J. Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization. Proc Natl Acad Sci U S A. 1978 May;75(5):2411–2415. doi: 10.1073/pnas.75.5.2411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maino V. C., Kurnick J. T., Kubo R. T., Grey H. M. Mitogen activation of human chronic lymphatic leukemia cells. I. Synthesis and secretion of immunoglobulin. J Immunol. 1977 Mar;118(3):742–748. [PubMed] [Google Scholar]
- Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
- Margulies D. H., Cieplinski W., Dharmgrongartama B., Gefter M. L., Morrison S. L., Kelly T., Scharff M. D. Regulation of immunoglobulin expression in mouse myeloma cells. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):781–791. doi: 10.1101/sqb.1977.041.01.089. [DOI] [PubMed] [Google Scholar]
- Margulies D. H., Kuehl W. M., Scharff M. D. Somatic cell hybridization of mouse myeloma cells. Cell. 1976 Jul;8(3):405–415. doi: 10.1016/0092-8674(76)90153-7. [DOI] [PubMed] [Google Scholar]
- Milstein C., Adetugbo K., Cowan N. J., Köhler G., Secher D. S., Wilde C. D. Somatic cell genetics of antibody-secreting cells: studies of clonal diversification and analysis by cell fusion. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):793–803. doi: 10.1101/sqb.1977.041.01.090. [DOI] [PubMed] [Google Scholar]
- Mohit B., Fan K. Hybrid cell line from a cloned immunoglobulin-producing mouse myeloma and a nonproducing mouse lymphoma. Science. 1971 Jan 8;171(3966):75–77. doi: 10.1126/science.171.3966.75. [DOI] [PubMed] [Google Scholar]
- Molinaro G. A., Dray S. Antibody coated erythrocytes as a manifold probe for antigens. Nature. 1974 Apr 5;248(448):515–517. doi: 10.1038/248515a0. [DOI] [PubMed] [Google Scholar]
- Morse H. C., 3rd, Neiders M. E., Lieberman R., Lawton A. R., 3rd, Asofsky R. Murine plasma cells secreting more than one class of immunoglobulin heavy chain. II. SAMM 368--a plasmacytoma secreting IgG2b-kappa and IgA-kappa immunoglobulins which do not share idiotypic determinants. J Immunol. 1977 May;118(5):1682–1689. [PubMed] [Google Scholar]
- Morse H. C., 3rd, Pumphrey J. G., Potter M., Asofsky R. Murine plasma cells secreting more than one class of immunoglobulin heavy chain. I. Frequency of two or more M-components in ascitic fluids from 788 primary plasmacytomas. J Immunol. 1976 Aug;117(2):541–547. [PubMed] [Google Scholar]
- NOSSAL G. J., SZENBERG A., ADA G. L., AUSTIN C. M. SINGLE CELL STUDIES ON 19S ANTIBODY PRODUCTION. J Exp Med. 1964 Mar 1;119:485–502. doi: 10.1084/jem.119.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nossal G. J., Warner N. L., Lewis H. Incidence of cells simultaneously secreting IgM and IgG antibody to sheep erythrocytes. Cell Immunol. 1971 Feb;2(1):41–53. doi: 10.1016/0008-8749(71)90024-4. [DOI] [PubMed] [Google Scholar]
- Pernis B., Forni L., Amante L. Immunoglobulin spots on the surface of rabbit lymphocytes. J Exp Med. 1970 Nov;132(5):1001–1018. doi: 10.1084/jem.132.5.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pernis B., Forni L., Amante L. Immunoglobulins as cell receptors. Ann N Y Acad Sci. 1971 Dec 31;190:420–431. doi: 10.1111/j.1749-6632.1971.tb13552.x. [DOI] [PubMed] [Google Scholar]
- Premkumar E., Potter M., Singer P. A., Sklar M. D. Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus-transformed lymphosarcoma cell lines. Cell. 1975 Oct;6(2):149–159. doi: 10.1016/0092-8674(75)90005-7. [DOI] [PubMed] [Google Scholar]
- Slavin S., Strober S. Spontaneous murine B-cell leukaemia. Nature. 1978 Apr 13;272(5654):624–626. doi: 10.1038/272624a0. [DOI] [PubMed] [Google Scholar]
- Wabl M. R., Forni L., Loor F. Switch in immunoglobulin class production observed in single clones of committed lymphocytes. Science. 1978 Mar 10;199(4333):1078–1080. doi: 10.1126/science.305113. [DOI] [PubMed] [Google Scholar]
- Weimann B. J. Induction of immunoglobulin synthesis in Abelson murine leukemia virus-transformed mouse lymphoma cells in culture. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):163–164. doi: 10.1101/sqb.1977.041.01.021. [DOI] [PubMed] [Google Scholar]
- Williamson A. R. Proliferation and differentiation of B lymphocytes: a model. Transplant Rev. 1975;23:258–265. [PubMed] [Google Scholar]
- Yelton D. E., Diamond B. A., Kwan S. P., Scharff M. D. Fusion of mouse myeloma and spleen cells. Curr Top Microbiol Immunol. 1978;81:1–7. doi: 10.1007/978-3-642-67448-8_1. [DOI] [PubMed] [Google Scholar]
- Zauderer M., Askonas B. A. Several proliferative phases precede maturation of IgG-secreting cells in mitogen-stimulated cultures. Nature. 1976 Apr 15;260(5552):611–613. doi: 10.1038/260611a0. [DOI] [PubMed] [Google Scholar]