Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Feb 1;153(2):324–338. doi: 10.1084/jem.153.2.324

Subclass-restricted IgG polyclonal antibody production in mice injected with lipid A-rich lipopolysaccharides

PMCID: PMC2186076  PMID: 7241048

Abstract

The effects of five distinct bacterial lipopolysaccharides (LPS) on the induction of polyclonal IgM and IgG antibodies, including polyclonal autoantibody formation, were investigated in several strains of mice. Injections of most LPS preparations that contained polysaccharide transiently induced only IgM polyclonal antibodies. However, LPS from Salmonella minnesota R595 (R595 LPS), which had a particularly high content of lipid A but lacked O-antigen polysaccharide, induced a markedly prolonged IgM and IgG polyclonal antibody response in mice, including athymic nude mice, but not in LPS-unresponsive C3H/HeJ mice. Polyclonal IgM and IgG production peaked in sera on day 8 and day 15, respectively, and remained higher than control values 2 mo after the injection. The IgG induced by R595 LPS was strictly restricted to IgG2b and Igg3 subclasses in normal mice. In contrast, in athymic nude mice which have normally lower levels of IgG1 and IgG2a than normal mice, R595 LPS stimulated the production of all the IgG subclasses and reconstituted serum levels of IgG1 and IgG2a up to, but not higher than, control values of normal mice. These findings suggest that different mechanisms regulate production of each IgG subclass after stimulation with LPS.

Full Text

The Full Text of this article is available as a PDF (840.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abney E. R., Cooper M. D., Kearney J. F., Lawton A. R., Parkhouse R. M. Sequential expression of immunoglobulin on developing mouse B lymphocytes: a systematic survey that suggests a model for the generation of immunoglobulin isotype diversity. J Immunol. 1978 Jun;120(6):2041–2049. [PubMed] [Google Scholar]
  2. Andersson J., Coutinho A., Melchers F. Stimulation of murine B lymphocytes to IgG synthesis and secretion by the mitogens lipopolysaccharide and lipoprotein and its inhibition by anti-immunoglobulin antibodies. Eur J Immunol. 1978 May;8(5):336–343. doi: 10.1002/eji.1830080509. [DOI] [PubMed] [Google Scholar]
  3. Andersson J., Sjöberg O., Möller G. Mitogens as probes for immunocyte activation and cellular cooperation. Transplant Rev. 1972;11:131–177. doi: 10.1111/j.1600-065x.1972.tb00048.x. [DOI] [PubMed] [Google Scholar]
  4. Apte R. N., Hertogs C. F., Pluznik D. H. Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. I. Relationship between colony-stimulating factor release and lymphocyte activation in vitro. J Immunol. 1977 Apr;118(4):1435–1440. [PubMed] [Google Scholar]
  5. Bankhurst A. D., Lambert P. H., Miescher P. A. Studies on the thymic dependence of the immunoglobulin classes of the mouse (38570). Proc Soc Exp Biol Med. 1975 Feb;148(2):501–504. doi: 10.3181/00379727-148-38570. [DOI] [PubMed] [Google Scholar]
  6. Commerford S. L. Iodination of nucleic acids in vitro. Biochemistry. 1971 May 25;10(11):1993–2000. doi: 10.1021/bi00787a005. [DOI] [PubMed] [Google Scholar]
  7. Coutinho A., Möller G. Thymus-independent B-cell induction and paralysis. Adv Immunol. 1975;21:113–236. doi: 10.1016/s0065-2776(08)60220-5. [DOI] [PubMed] [Google Scholar]
  8. David G. S., Reisfeld R. A. Protein iodination with solid state lactoperoxidase. Biochemistry. 1974 Feb 26;13(5):1014–1021. doi: 10.1021/bi00702a028. [DOI] [PubMed] [Google Scholar]
  9. Eckels D. D., Gershwin M. E., Drago J., Faulkin L. Comparative patterns of serum immunoglobulin levels in specific-pathogen-free congenitally athymic (nude), hereditarily asplenic (Dh/+), congenitally athymic-asplenic (lasat) and splenectomized athymic mice. Immunology. 1979 Aug;37(4):777–783. [PMC free article] [PubMed] [Google Scholar]
  10. Fournié G. J., Lambert P. H., Meischer P. A. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. doi: 10.1084/jem.140.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  12. Gronowicz E., Coutinho A. Selective triggering of B cell subpopulations by mitogens. Eur J Immunol. 1974 Nov;4(11):771–776. doi: 10.1002/eji.1830041113. [DOI] [PubMed] [Google Scholar]
  13. Hammerling U., Chin A. F., Abbott J., Scheid M. P. The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes. J Immunol. 1975 Nov;115(5):1425–1431. [PubMed] [Google Scholar]
  14. Ishikawa H., Saito K. Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity. J Exp Med. 1980 Apr 1;151(4):965–968. doi: 10.1084/jem.151.4.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Izui S., Eisenberg R. A., Dixon F. J. IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides. J Immunol. 1979 May;122(5):2096–2102. [PubMed] [Google Scholar]
  16. Izui S., Kobayakawa T., Louis J., Lambert P. H. Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice. Eur J Immunol. 1979 Apr;9(4):338–341. doi: 10.1002/eji.1830090416. [DOI] [PubMed] [Google Scholar]
  17. Izui S., Kobayakawa T., Zryd M. J., Louis J., Lambert P. H. Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice; II. Correlation between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators. J Immunol. 1977 Dec;119(6):2157–2162. [PubMed] [Google Scholar]
  18. Izui S., Lambert P. H., Fournié G. J., Türler H., Miescher P. A. Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes. J Exp Med. 1977 May 1;145(5):1115–1130. doi: 10.1084/jem.145.5.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Izui S., Lambert P. H., Miescher P. A. Determination of anti-DNA antibodies by a modified 125I-labelled DNA-binding test. Elimination of non-specific binding of DNA to non-immunoglobulin basic proteins by using an anionic detergent. Clin Exp Immunol. 1976 Dec;26(3):425–430. [PMC free article] [PubMed] [Google Scholar]
  20. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  21. Izui S., Morrison D. C., Curry B., Dixon F. J. Effect of lipid A-associated protein and lipid A on the expression of lipopolysaccharide activity. I. Immunological activity. Immunology. 1980 Jul;40(3):473–482. [PMC free article] [PubMed] [Google Scholar]
  22. Izui S., Zaldivar N. M., Scher I., Lambert P. H. Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. I. Anti-DNA induction by LPS without significant release of DNA in circulating blood. J Immunol. 1977 Dec;119(6):2151–2156. [PubMed] [Google Scholar]
  23. Kettman J., Dutton R. W. An in vitro primary immune response to 2,4,6-trinitrophenyl substituted erythrocytes: response against carrier and hapten. J Immunol. 1970 Jun;104(6):1558–1561. [PubMed] [Google Scholar]
  24. Kolb C., Di Pauli R., Weiler E. Induction of IgG in young nude mice by lipid A or thymus grafts. J Exp Med. 1976 Oct 1;144(4):1031–1036. doi: 10.1084/jem.144.4.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. McAdam K. P., Sipe J. D. Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein. J Exp Med. 1976 Oct 1;144(4):1121–1127. doi: 10.1084/jem.144.4.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  28. Perlmutter R. M., Hansburg D., Briles D. E., Nicolotti R. A., Davie J. M. Subclass restriction of murine anti-carbohydrate antibodies. J Immunol. 1978 Aug;121(2):566–572. [PubMed] [Google Scholar]
  29. Scheid M. P., Hoffmann M. K., Komuro K., Hämmerling U., Abbott J., Boyse E. A., Cohen G. H., Hooper J. A., Schulof R. S., Goldstein A. L. Differentiation of T cells induced by preparations from thymus and by nonthymic agents. J Exp Med. 1973 Oct 1;138(4):1027–1032. doi: 10.1084/jem.138.4.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Skidmore B. J., Chiller J. M., Morrison D. C., Weigle W. O. Immunologic properties of bacterial lipopolysaccharide (LPS): correlation between the mitogenic, adjuvant, and immunogenic activities. J Immunol. 1975 Feb;114(2 Pt 2):770–775. [PubMed] [Google Scholar]
  31. Sultzer B. M. Genetic control of leucocyte responses to endotoxin. Nature. 1968 Sep 21;219(5160):1253–1254. doi: 10.1038/2191253a0. [DOI] [PubMed] [Google Scholar]
  32. Ulevitch R. J. The preparation and characterization of a radioiodinated bacterial lipopolysaccharide. Immunochemistry. 1978 Mar;15(3):157–164. doi: 10.1016/0161-5890(78)90144-x. [DOI] [PubMed] [Google Scholar]
  33. Watson J., Riblet R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1147–1161. doi: 10.1084/jem.140.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES