Abstract
B lymphoblasts immortalized by the Epstein-Barr virus (EBV) exhibit autocrine growth stimulation--that is they release a soluble activity to which they respond by growth. A minimally supplemented serum-free medium conditioned by lymphoblastoid cells in their log phase of growth (LCL-CM) was found to contain autostimulatory activity allowing us to explore the mechanism of autocrine growth for these cell-types in defined conditions. Below cell densities capable of supporting autonomous growth, continued proliferation in serum-free medium was dependent on both added LCL-CM and transferrin. Neither activity alone was capable of sustaining growth. At higher cell densities, transferrin by itself was sufficient to maintain the autocrine loop. The action of the autostimulatory factor appeared to reside in its ability to prime cells continually for a proliferative response to transferrin by enhancing the expression of transferrin receptors at the lymphoblast surfaces. The implications of these findings for normal B cell physiology and their possible relation to oncogenesis are discussed.
Full Text
The Full Text of this article is available as a PDF (390.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anzano M. A., Roberts A. B., Smith J. M., Sporn M. B., De Larco J. E. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6264–6268. doi: 10.1073/pnas.80.20.6264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blazar B. A., Sutton L. M., Strome M. Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr virus. Cancer Res. 1983 Oct;43(10):4562–4568. [PubMed] [Google Scholar]
- Brock J. H. The effect of iron and transferrin on the response of serum-free cultures of mouse lymphocytes to concanavalin A and lipopolysaccharide. Immunology. 1981 Jun;43(2):387–392. [PMC free article] [PubMed] [Google Scholar]
- Gordon J., Mellstedt H., Aman P., Biberfeld P., Björkholm M., Klein G. Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings. Blood. 1983 Oct;62(4):910–917. [PubMed] [Google Scholar]
- Goubin G., Goldman D. S., Luce J., Neiman P. E., Cooper G. M. Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA. Nature. 1983 Mar 10;302(5904):114–119. doi: 10.1038/302114a0. [DOI] [PubMed] [Google Scholar]
- Howard M., Paul W. E. Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol. 1983;1:307–333. doi: 10.1146/annurev.iy.01.040183.001515. [DOI] [PubMed] [Google Scholar]
- Kaplan P. L., Anderson M., Ozanne B. Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system. Proc Natl Acad Sci U S A. 1982 Jan;79(2):485–489. doi: 10.1073/pnas.79.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilsson K., Klein G. Phenotypic and cytogenetic characteristics of human B-lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma. Adv Cancer Res. 1982;37:319–380. doi: 10.1016/s0065-230x(08)60886-6. [DOI] [PubMed] [Google Scholar]
- Novogrodsky A., Ravid A., Glaser T., Rubin A. L., Stenzel K. H. Role of iron in transferrin-dependent lymphocyte mitogenesis in serum-free medium. Exp Cell Res. 1982 Jun;139(2):419–422. doi: 10.1016/0014-4827(82)90270-1. [DOI] [PubMed] [Google Scholar]
- Ohno S., Yazaki A. Simple construction of human c-myc gene implicated in B-cell neoplasmas and its relationship with avian v-myc and human lymphokines. Scand J Immunol. 1983 Nov;18(5):373–388. doi: 10.1111/j.1365-3083.1983.tb00869.x. [DOI] [PubMed] [Google Scholar]
- Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
- Uittenbogaart C. H., Fahey J. L. Leukemia-derived growth factor (non-interleukin 2) produced by a human malignant T lymphoid cell line. Proc Natl Acad Sci U S A. 1982 Nov;79(22):7004–7008. doi: 10.1073/pnas.79.22.7004. [DOI] [PMC free article] [PubMed] [Google Scholar]