Skip to main content

Lymphocyte Activation by Endotoxin and Endotoxin Protein

The Role of the C3H/HeJ Mouse

  • Chapter
Beneficial Effects of Endotoxins

Abstract

A perusal of the literature on endotoxins in the past decade makes it clear that a renewed interest has developed to explain the multiple pathophysiological and immunological host responses to lipopolysac-charide endotoxin (LPS). In great measure this was due to the recognition that many of these responses were under genetic control. The genetic approach taken by numerous workers arose from the discovery of the mutant C3H/HeJ mouse strain, which is highly resistant to the toxic effects of LPS and which displays cellular responses both in vivo and in vitro that are diametrically opposite to those from normally susceptible mice (Sultzer, 1968, 1969). The availability of this inbred strain gave rise to a variety of comparative studies so that a rather extensive literature on this subject has accumulated and continues to do so. However, within the allotted space for this article, I will only attempt to highlight those aspects of the work with this strain that have dealt with the activation of lymphocytes by LPS, and to discuss in some detail the newer studies originating from the use of the C3H/HeJ mouse that have established that various proteins associated with the LPS in the outer membrane of gram-negative bacteria are potent activators of immunocompetent cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Andersson, J., Möller, G., and Sjöbcrg, O., 1972a, Selective induction of DNA synthesis in T and B lymphocytes, Cell. Immunol. 4:381.

    Article  PubMed  CAS  Google Scholar 

  • Andersson, J., Sjöberg, O., and Möller, G., 1972b, Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides, Eur. J. Immunol. 2:349.

    Article  PubMed  CAS  Google Scholar 

  • Andersson, J., Coutinho, A., and Melchers, F., 1977, Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages, J Exp. Med. 145:1511.

    Article  PubMed  CAS  Google Scholar 

  • Betz, S. J., and Morrison, D. C., 1977, Chemical and biological properties of a protein rich fraction of bacterial lipopolysaccharides. I. The in vitro murine lymphocyte response, J. Immunol. 119:1475.

    PubMed  CAS  Google Scholar 

  • Bick, P. H., Persson, U., Smith, E., Möller, G., and Hammarström, L., 1977, Genetic control of lymphocyte activation: Lack of response to low doses of concanavalin A in lipopolysaccharide-nonresponder mice, J. Exp. Med. 146:1146.

    Article  PubMed  CAS  Google Scholar 

  • Braley-Mullen, H., Hayes, N., and Sanders, M., 1977, Suppression of IgM responses to type III pneumococcal polysaccharide by lipopolysaccharide (LPS), Cell. Immunol. 30: 300.

    Article  PubMed  CAS  Google Scholar 

  • Braun, V., 1977, Lipoprotein from the outer membrane of Escherichia coli as an antigen, immunogen, and mitogen, in: Microbiology 1977 (D. Schlessinger, ed.), pp. 251–261, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Chedid, L., and LeGarrec, Y., 1980, Transfer of cells or of serum factors in nonspecific resistance to infection, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 19–24, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Coutinho, A., 1976, Genetic control of B-cell responses. II. Identification of the spleen B-cell defect in C3H/HeJ mice, Scand. J. Immunol. 5:129.

    Article  PubMed  CAS  Google Scholar 

  • Coutinho, A., and Meo, T., 1978, Genetic basis for unresponsiveness to lipopolysaccha-ride in C57B1/10/Cr mice, Immunogenetics 7:17–24.

    Article  PubMed  CAS  Google Scholar 

  • Coutinho, A., Forni, L., and Watanabe, T., 1978, Genetic and functional characterization of an antiserum to the lipid-A-specific triggering receptor on murine B-cells, Eur. J. Immunol. 8:63.

    Article  PubMed  CAS  Google Scholar 

  • Eisenstein, T. K., and Angerman, C. R., 1978, Studies on the protective capacity and immunogenicity of lipopolysaccharide, acetone-killed cells, and a ribosome-rich extract of Salmonella typhimunum in C3H/HeJ and CD-I mice, J. Immunol. 121:1010.

    PubMed  CAS  Google Scholar 

  • Eisenstein, T. K., and Sultzer, B. M., 1981, Salmonella vaccines: Protection by endotoxin protein and lipopolysaccharide in two different mouse strains, in: Bacterial Vaccines, Vol. 4.(J. Robbins, J. Hill, and J. Sadoff, eds.), pp. 423–128, Thieme-Stratton, New York.

    Google Scholar 

  • Eisenstein, T. K., Deakins, L. W., and Sultzer, B. M., 1980, The C3HeB/FeJ mouse, a strain in the C3H lineage which separates Salmonella susceptibility and immunizability from mitogenic responsiveness to lipopolysaccharide, in: Genetic Control of Natural Resistance to Infection and Malignancy (E. Shamere, P. A. R. Kongsharer, and M. Landy, eds.), pp. 115–120, Academic Press, New York.

    Google Scholar 

  • Esquivei, P. S., Kong, Y. M., and Rose, N. R., 1978, Evidence for thyroglobulin-reactive T cells in good responder mice, Cell. Immunol. 37:14.

    Article  Google Scholar 

  • Forni, L., and Coutinho, A., 1978, An antiserum which recognizes lipopolysaccharide-re-active B cells in the mouse, Eur. J. Immunol. 8:56.

    Article  PubMed  CAS  Google Scholar 

  • Gery, I., Kruger, J., and Spiesel, S. Z., 1972, Stimulation of B-lymphocytes by endotoxin: Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T6T6 thymus grafts, J Immunol. 108:1088.

    PubMed  CAS  Google Scholar 

  • Glode, L. M., and Rosenstreich, D. L., 1976, Genetic control of B cell activation by bacterial lipopolysaccharide is mediated by multiple distinct genes or alleles, J. Immunol. 117:2061.

    PubMed  CAS  Google Scholar 

  • Glode, L. M., Mergenhagen, S. E., and Rosenstreich, D. L., 1976, Significant contribution of spleen cells in meditating the lethal effects of endotoxin in vivo, Infect. Immun. 14:626.

    PubMed  CAS  Google Scholar 

  • Goodman, G. W., and Sultzer, B. M., 1979a, Further studies on the activation of lymphocytes by endotoxin protein, J. Immunol. 122:1329.

    PubMed  CAS  Google Scholar 

  • Goodman, G. W., and Sultzer, B. M., 1979b, Endotoxin protein is a mitogen and polyclonal activator of human B-lymphocytes, J. Exp. Med. 149:713.

    Article  PubMed  CAS  Google Scholar 

  • Goodman, G. W., and Sultzer, B. M., 1979c, Characterization of the chemical and physical properties of a novel B-lymphocyte activator, endotoxin protein, Infect. Immun. 24:685.

    PubMed  CAS  Google Scholar 

  • Goodman, M. G., and Weigle, W. O., 1979, T-Cell regulation of polyclonal B-cell responses. I. Helper effects of T-cells, J Immunol. 122:2548.

    PubMed  CAS  Google Scholar 

  • Goodman, M. G., Parks, D. E., and Weigle, W. O., 1978, Immunologic responsiveness of the C3H/HeJ mouse: Differential ability of the butanol-extracted lipopolysaccharide (LPS) to evoke LPS-mediated effects, J Exp. Med. 147:800.

    Article  PubMed  CAS  Google Scholar 

  • Gregory, S. H., Zimmerman, D. H., and Kern, M., 1980, The lipid A moiety of lipopolysaccharide is specifically bound to B-cell subpopulations of responder and nonresponder animals, J Immunol. 125:102.

    PubMed  CAS  Google Scholar 

  • Hämmerling, I., Chin, A. F., Abbot, J., and Scheid, M. C., 1975, The ontogeny of murine B-lymphocytes. I. Induction of phenotypic conversion of la to Ia+ lymphocytes, J. Immunol. 115:1425.

    PubMed  Google Scholar 

  • Hoffman, M. K., Galanos, C., Koenig, S., and Oettgen, H. F., 1977, B-Cell activation by lipopolysaccharide: Distinct pathways for induction of mitosis and antibody production, J. Exp. Med. 146:1640.

    Article  Google Scholar 

  • Kabir, S., and Rosenstreich, D. L., 1977, Binding of bacterial endotoxin to murine spleen lymphocytes, Infect. Immun. 15:156.

    PubMed  CAS  Google Scholar 

  • Kong, Y. M., El-Rehewy, M., Giraldo, A. A., Esquivei, P. S., Jeffries, C. D., Rose, N. R., and David, C. S., 1978, The effect of LPS responsiveness on induction of autoimmune thyroiditis, Fed. Proc. 37:1380.

    Google Scholar 

  • Kreisler, J. M., and Möller, G., 1974, Effect of PPD on the specific immune response to heterologous red cells in vitro, J. Immunol. 112:151.

    CAS  Google Scholar 

  • Kuusi, N., Nurminen, M., Saxen, H., Valtonen, M., and Makela, P. H., 1979, Immunization with major outer membrane proteins in experimental salmonellosis of mice, Infect. Immun. 25:857.

    PubMed  CAS  Google Scholar 

  • Levy, G. A., and Edgington, T. S., 1980, Lymphoid procoagulant activity and mitogenesis in the G3H/HeJ mouse: Discordant response to lipopolysaccharide stimulation, J. Immunol. 124:2665.

    PubMed  CAS  Google Scholar 

  • Männel, D. N., Rosenstreich, D. L., and Mergenhagen, S. E., 1979, Mechanism of lipo-polysaccharidc-induced tumor necrosis: Requirement for lipopolysaccharide sensitive lymphoreticular cells, Infect. Immun. 24:573.

    PubMed  Google Scholar 

  • Melchers, F., 1977, B lymphocyte development in fetal liver. I. Development of reactivities to B-cell mitogens in vivo and in vitro, Eur. J. Immunol. 7:476.

    Article  CAS  Google Scholar 

  • Morrison, D. C., and Betz, S. J., 1977, Ghemical and biological properties of a protein rich fraction of bacterial lipopolysaccharide. II. The in vitro peritoneal mast cell response, J. Immunol. 119:1790.

    CAS  Google Scholar 

  • Morrison, D. C., and Leive, L. 1975, Fractions of lipopolysaccharide from Escherichia coli Ol 11:B4 prepared by two extraction procedures, J. Biol. Chem. 250:2911.

    PubMed  CAS  Google Scholar 

  • Morrison, D. C., and Ryan, J. L., 1979, Bacterial endotoxins and host immune responses, Adv. Immunol. 28:294.

    Google Scholar 

  • Morrison, D. C., Betz, S. J., and Jacobs, D. M., 1976, Isolation of a lipid A bound polypeptide responsible for “LPS-initiated” mitogenesis of C3H/HeJ spleen cells, J. Exp. Med. 144:840.

    Article  PubMed  CAS  Google Scholar 

  • Morrison, D. C., Wilson, M. E., Razuiddin, S., Betz, S. J., Gurry, B. J., Dades, Z., and Munkenbeck, P., 1980, Influence of lipid A-associated protein on endotoxin stimulation of nonlymphoid cells, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 30–35, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Nilsson, B. S., Sultzer, B. M., and Bullock, W. W., 1973, Purified protein derivative of tuberculin induces immunoglobulin production in normal mouse spleen cells, J. Exp. Med. 137:127.

    Article  PubMed  CAS  Google Scholar 

  • Norcross, M. A., and Smith, R. T., 1977, Regulation of B-cell proliferative responses to lipopolysaccharide by a subclass of thymus T-cells, J. Exp. Med. 145:1299.

    Article  PubMed  CAS  Google Scholar 

  • Nygren, H., Dahlen, G., and Möller, G., 1979, Bacterial lipopolysaccharides bind selectively to lymphocytes from lipopolysaccharide high-responder mouse strains, Scand. J. Immunol. 10:555.

    Article  PubMed  CAS  Google Scholar 

  • Peavy, D. L., Adler, W. H., and Smith, R. T., 1970, The mitogenic effects of endotoxin and staphylococcal enterotoxin B on mouse spleen cells and human peripheral lymphocytes, J. Immunol. 105:1453.

    CAS  Google Scholar 

  • Primi, D., Hammarström, L., Möller, G., Smith, C. I. E., and Uhr, J., 1979, Gon-A-activated T-cells scerete factors with polyclonal B-cell-activating properties, Scand. J. Immunol. 9:467.

    Article  PubMed  CAS  Google Scholar 

  • Rosenstreich, D. L., and McAdam, K. P. W. J., 1979, Lymphoid cells in endotoxin-induced production of the amyloid-related serum amyloid A protein, Inject. Immun. 23: 181.

    CAS  Google Scholar 

  • Rosenstreich, D. L., Glode, L. M., Wahl, L. M., Sandberg, A. L., and Mcrgenhagen, S. E., 1977, Analysis of the cellular defects of endotoxin-unresponsive C3H/HeJ mice, in: Microbiology 1977 (D. Schlessinger, ed.), pp. 314–320, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Rudbach, J. A., and Reed, N. D., 1977, Immunological responses of mice to lipopolysac-charide: Lack of secondary responsiveness by C3H/HeJ mice, Infect. Immun. 16:513.

    PubMed  CAS  Google Scholar 

  • Skidmore, B. J., Morrison, D. C., Chiller, J. M., and Weigle, W. O., 1975, Immunologic properties of bacterial lipopolysaccharide (LPS). II. The unresponsiveness of C3H/HeJ mouse spleen cells to LPS-induced mitogenesis is dependent on the method used to extract LPS, J. Exp. Med. 142:1488.

    Article  PubMed  CAS  Google Scholar 

  • Skidmore, B. J., Chiller, J. M., and Weigle, W. O., 1977, Immunologic properties of bacterial lipopolysaccharide (LPS). IV. Cellular basis of the unresponsiveness of C3H/HeJ mouse spleen cells to LPS-induced mitogenesis, J. Immunol. 118:274.

    PubMed  CAS  Google Scholar 

  • Slowe, A., and Waldmann, H., 1975, The “intrinsic adjuvanticity” and immunogenicity of trinitrophenylated lipopolysaccharide, Immunology 29:825.

    PubMed  CAS  Google Scholar 

  • Sultzer, B. M., 1968, Genetic control of leucocyte responses to endotoxin, Nature (London) 219:1253.

    Article  CAS  Google Scholar 

  • Sultzer, B. M., 1969, Genetic factors in leucocyte responses to endotoxin: Further studies in mice, J. Immunol. 103:32.

    PubMed  CAS  Google Scholar 

  • Sultzer, B. M., 1972, Genetic control of host responses to endotoxin, Infect. Immun. 5:107.

    PubMed  CAS  Google Scholar 

  • Sultzer, B. M., 1973, Mitogenic and immune responses to endotoxin: A deficiency in C3H/HeJ mice, Abstr. Annu. Meet. Am. Soc. Microbiol. p. 85, M69.

    Google Scholar 

  • Sultzer, B. M., 1976, Genetic analysis oflymphocyte activation by lipopolysaccharide endotoxin, Infect. Immun. 13:1579.

    PubMed  CAS  Google Scholar 

  • Sultzer, B. M., and Goodman, G. W., 1976, Endotoxin protein: A B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes, J. Exp. Med. 144:821.

    Article  CAS  Google Scholar 

  • Sultzer, B. M., and Nilsson, B. S., 1972, PPD-tuberculin—A B-cell mitogen, Sature Sew Biol. 240:198.

    CAS  Google Scholar 

  • Sultzer, B. M., Nilsson, B. S., and Kirschenbaum, D., 1977, Nonspecific stimulation of lymphocytes by tuberculin, Inject. Immun. 15:799.

    CAS  Google Scholar 

  • Sultzer, B. M., Goodman, G. W., and Eisenstein, T. K., 1980, Endotoxin protein as an immunostimulant, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 61–65, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Symons, D. B. A., and Clarkson, C. A., 1979, The binding of LPS to the lymphocyte surface, Immunology 38:503.

    PubMed  CAS  Google Scholar 

  • Tanabe, M. J., and Nakano, M., 1979a, Dysfunction of thymocytes of C3H/HeJ mice in blastogenic response to antithymocyte serum in vitro and its repair with lipopolysaccharide induced mediator, Microbiol. Immunol. 23:287.

    PubMed  CAS  Google Scholar 

  • Tanabe, M. J., and Nakano, M., 1979b, Lipopolysaccharide-induced mediators assisting the proliferative response of C3H/HeJ thymocytes to concanavalin A, Microbiol. Immunol. 23:1097.

    PubMed  CAS  Google Scholar 

  • Vallera, D. A., Gamble, C. E., and Schmidtke, J. R., 1980, Lipopolysaccharide-induced immunomodulation of the generation cell-mediated cytoxicity. II. Evidence for the involvement of a regulatory B lymphocyte, J. Immunol. 124:641.

    PubMed  CAS  Google Scholar 

  • Watanabe, T., and Ohara, J., 1981, Functional nuclei of LPS-nonrespondcr C3H/HeJ mice after transfer into LPS-responder C3H/HeN cells by cell fusion, Nature (London) 290:58.

    Article  CAS  Google Scholar 

  • Watson, J., 1977, Differentiation of B lymphocytes in C3H/HeJ mice: The induction of la antigens by lipopolysaccharide, J. Immunol. 118:1103.

    PubMed  CAS  Google Scholar 

  • Watson, J., and Riblet, R., 1974, Genetic control of responses to bacterial lipopolysaccharide in mice. I. Evidence for a single gene that influences mitogenic and immunogenic responses to lipopolysaccharides, J. Exp. Med. 140:1147.

    Article  PubMed  CAS  Google Scholar 

  • Watson, J., and Riblet, R., 1975, Genetic control of responses to bacterial lipopoly-saccharides in mice. II. A gene that influences the activity of a membrane receptor for lipopolysaccharides, J. Immunol. 114:1462.

    PubMed  CAS  Google Scholar 

  • Watson, J., Riblet, R., and Taylor, B., 1977, The response to lipopolysaccharides in recombinant inbred lines of mice, J Immunol. 118:1604.

    Google Scholar 

  • Watson, J., Kelly, K., Largen, M., and Taylor, B. A., 1978a, The genetic mapping of defective LPS response gene in C3H/HeJ mice, J. Immunol. 120:422.

    PubMed  CAS  Google Scholar 

  • Watson, J., Largen, M., McAdam, K. P. W. J., and Taylor, B. A., 1978b, Genetic control of endotoxic responses in mice, J. Exp. Med. 147:39.

    Article  PubMed  CAS  Google Scholar 

  • Watson, J., Kelly, K., and Whitlock, C., 1980, Genetic control of endotoxin sensitivity, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 4–10, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Yoshida, T., Hidekichi, S., and Cohen, S., 1973, The protection of migration inhibition factor by B and T cells of the guinea pig, J. Exp. Med. 38:784.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Plenum Press, New York

About this chapter

Cite this chapter

Sultzer, B.M. (1983). Lymphocyte Activation by Endotoxin and Endotoxin Protein. In: Nowotny, A. (eds) Beneficial Effects of Endotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4364-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-4364-6_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-4366-0

  • Online ISBN: 978-1-4684-4364-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics