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. 1995 Jul;63(7):2596–2603. doi: 10.1128/iai.63.7.2596-2603.1995

Single exposure of mice to Borrelia burgdorferi elicits immunoglobulin G antibodies characteristic of secondary immune response without production of interleukin-4 by immune T cells.

A B Frey 1, T D Rao 1
PMCID: PMC173348  PMID: 7790074

Abstract

Borrelia burgdorferi antigen can elicit immunoglobulins (Igs) characteristic of the primary and secondary immune responses without the contribution of an interleukin-4-producing helper T-cell population. Single exposure of mice to soluble B. burgdorferi antigen elicited both Th1-type and Th2-type antispirochete antibodies. Production of the Ig classes showed different patterns with increasing time postinjection (IgM levels decreased; IgG1, IgG2a, IgG2b, and IgG3 levels increased; IgE was not detected), and Ig patterns were similar to those produced in infected mice. Upon infectious challenge, immunized mice achieved maximal titers of all antispirochete IgG subclasses more quickly than unimmunized mice did. In contrast to the antibody responses which showed both Th1- and Th2-type patterns, T-cell immune response to either immunization or infection was characterized by interleukin-2 and gamma interferon production; interleukin-4 and interleukin-5 were undetectable. Injection with whole spirochetes induced a pattern of antibodies and cytokine production similar to those obtained by injection with soluble antigen. In addition, mouse strains of different major histocompatibility complex backgrounds produced similar patterns of Ig in response to immunization. None of the various parameters of immunization tested resulted in detectable interleukin-4 production by primary or secondary immune T cells. The production of both IgM and IgG1 at early times following a single exposure to spirochete antigen clearly differs from immune responses to haptens or model protein antigens. Production of similar Ig classes in infected and immune mice implies that antigen-specific antibody is responsible for passive immunizing activity found in immune sera.

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Selected References

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  1. Abehsira-Amar O., Gibert M., Joliy M., Thèze J., Jankovic D. L. IL-4 plays a dominant role in the differential development of Tho into Th1 and Th2 cells. J Immunol. 1992 Jun 15;148(12):3820–3829. [PubMed] [Google Scholar]
  2. Allison A. C., Harington J. S., Birbeck M. An examination of the cytotoxic effects of silica on macrophages. J Exp Med. 1966 Aug 1;124(2):141–154. doi: 10.1084/jem.124.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bachmann M. F., Rohrer U. H., Kündig T. M., Bürki K., Hengartner H., Zinkernagel R. M. The influence of antigen organization on B cell responsiveness. Science. 1993 Nov 26;262(5138):1448–1451. doi: 10.1126/science.8248784. [DOI] [PubMed] [Google Scholar]
  4. Barthold S. W., Bockenstedt L. K. Passive immunizing activity of sera from mice infected with Borrelia burgdorferi. Infect Immun. 1993 Nov;61(11):4696–4702. doi: 10.1128/iai.61.11.4696-4702.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barthold S. W., de Souza M. S., Janotka J. L., Smith A. L., Persing D. H. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993 Sep;143(3):959–971. [PMC free article] [PubMed] [Google Scholar]
  6. Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. doi: 10.1016/0167-5699(88)91308-4. [DOI] [PubMed] [Google Scholar]
  7. Bradley L. M., Duncan D. D., Tonkonogy S., Swain S. L. Characterization of antigen-specific CD4+ effector T cells in vivo: immunization results in a transient population of MEL-14-, CD45RB- helper cells that secretes interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma. J Exp Med. 1991 Sep 1;174(3):547–559. doi: 10.1084/jem.174.3.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bradley L. M., Duncan D. D., Yoshimoto K., Swain S. L. Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen. J Immunol. 1993 Apr 15;150(8 Pt 1):3119–3130. [PubMed] [Google Scholar]
  9. Bundoc V. G., Barbour A. G. Clonal polymorphisms of outer membrane protein OspB of Borrelia burgdorferi. Infect Immun. 1989 Sep;57(9):2733–2741. doi: 10.1128/iai.57.9.2733-2741.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Callister S. M., Schell R. F., Case K. L., Lovrich S. D., Day S. P. Characterization of the borreliacidal antibody response to Borrelia burgdorferi in humans: a serodiagnostic test. J Infect Dis. 1993 Jan;167(1):158–164. doi: 10.1093/infdis/167.1.158. [DOI] [PubMed] [Google Scholar]
  11. Coleman J. L., Rogers R. C., Benach J. L. Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB. Infect Immun. 1992 Aug;60(8):3098–3104. doi: 10.1128/iai.60.8.3098-3104.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
  13. Fikrig E., Barthold S. W., Marcantonio N., Deponte K., Kantor F. S., Flavell R. A. Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice. Infect Immun. 1992 Feb;60(2):657–661. doi: 10.1128/iai.60.2.657-661.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Finkelman F. D., Holmes J., Katona I. M., Urban J. F., Jr, Beckmann M. P., Park L. S., Schooley K. A., Coffman R. L., Mosmann T. R., Paul W. E. Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol. 1990;8:303–333. doi: 10.1146/annurev.iy.08.040190.001511. [DOI] [PubMed] [Google Scholar]
  15. Firestein G. S., Roeder W. D., Laxer J. A., Townsend K. S., Weaver C. T., Hom J. T., Linton J., Torbett B. E., Glasebrook A. L. A new murine CD4+ T cell subset with an unrestricted cytokine profile. J Immunol. 1989 Jul 15;143(2):518–525. [PubMed] [Google Scholar]
  16. Hayakawa K., Hardy R. R. Phenotypic and functional alteration of CD4+ T cells after antigen stimulation. Resolution of two populations of memory T cells that both secrete interleukin 4. J Exp Med. 1989 Jun 1;169(6):2245–2250. doi: 10.1084/jem.169.6.2245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  18. Hughes C. A., Engstrom S. M., Coleman L. A., Kodner C. B., Johnson R. C. Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB. Infect Immun. 1993 Dec;61(12):5115–5122. doi: 10.1128/iai.61.12.5115-5122.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnson R. C., Kodner C., Russell M., Duray P. H. Experimental infection of the hamster with Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:258–263. doi: 10.1111/j.1749-6632.1988.tb31859.x. [DOI] [PubMed] [Google Scholar]
  20. Johnson R. C., Kodner C., Russell M. Passive immunization of hamsters against experimental infection with the Lyme disease spirochete. Infect Immun. 1986 Sep;53(3):713–714. doi: 10.1128/iai.53.3.713-714.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kelso A., Gough N. M. Coexpression of granulocyte-macrophage colony-stimulating factor, gamma interferon, and interleukins 3 and 4 is random in murine alloreactive T-lymphocyte clones. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9189–9193. doi: 10.1073/pnas.85.23.9189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kochi S. K., Johnson R. C., Dalmasso A. P. Facilitation of complement-dependent killing of the Lyme disease spirochete, Borrelia burgdorferi, by specific immunoglobulin G Fab antibody fragments. Infect Immun. 1993 Jun;61(6):2532–2536. doi: 10.1128/iai.61.6.2532-2536.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ma Y., Weis J. J. Borrelia burgdorferi outer surface lipoproteins OspA and OspB possess B-cell mitogenic and cytokine-stimulatory properties. Infect Immun. 1993 Sep;61(9):3843–3853. doi: 10.1128/iai.61.9.3843-3853.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mohler K. M., Butler L. D. Differential production of IL-2 and IL-4 mRNA in vivo after primary sensitization. J Immunol. 1990 Sep 15;145(6):1734–1739. [PubMed] [Google Scholar]
  25. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  26. Sadziene A., Thompson P. A., Barbour A. G. In vitro inhibition of Borrelia burgdorferi growth by antibodies. J Infect Dis. 1993 Jan;167(1):165–172. doi: 10.1093/infdis/167.1.165. [DOI] [PubMed] [Google Scholar]
  27. Schaible U. E., Kramer M. D., Eichmann K., Modolell M., Museteanu C., Simon M. M. Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc Natl Acad Sci U S A. 1990 May;87(10):3768–3772. doi: 10.1073/pnas.87.10.3768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schmitz J. L., Schell R. F., Callister S. M., Lovrich S. D., Day S. P., Coe J. E. Immunoglobulin G2 confers protection against Borrelia burgdorferi infection in LSH hamsters. Infect Immun. 1992 Jul;60(7):2677–2682. doi: 10.1128/iai.60.7.2677-2682.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schmitz J. L., Schell R. F., Lovrich S. D., Callister S. M., Coe J. E. Characterization of the protective antibody response to Borrelia burgdorferi in experimentally infected LSH hamsters. Infect Immun. 1991 Jun;59(6):1916–1921. doi: 10.1128/iai.59.6.1916-1921.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schoenfeld R., Araneo B., Ma Y., Yang L. M., Weis J. J. Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi. Infect Immun. 1992 Feb;60(2):455–464. doi: 10.1128/iai.60.2.455-464.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schwan T. G., Kime K. K., Schrumpf M. E., Coe J. E., Simpson W. J. Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi). Infect Immun. 1989 Nov;57(11):3445–3451. doi: 10.1128/iai.57.11.3445-3451.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sigal L. H., Steere A. C., Dwyer J. M. In vivo and in vitro evidence of B cell hyperactivity during Lyme disease. J Rheumatol. 1988 Apr;15(4):648–654. [PubMed] [Google Scholar]
  33. Simpson W. J., Burgdorfer W., Schrumpf M. E., Karstens R. H., Schwan T. G. Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals. J Clin Microbiol. 1991 Feb;29(2):236–243. doi: 10.1128/jcm.29.2.236-243.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Steere A. C. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. doi: 10.1056/NEJM198908313210906. [DOI] [PubMed] [Google Scholar]
  35. Swain S. L., Bradley L. M., Croft M., Tonkonogy S., Atkins G., Weinberg A. D., Duncan D. D., Hedrick S. M., Dutton R. W., Huston G. Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. Immunol Rev. 1991 Oct;123:115–144. doi: 10.1111/j.1600-065x.1991.tb00608.x. [DOI] [PubMed] [Google Scholar]
  36. Vitetta E. S., Berton M. T., Burger C., Kepron M., Lee W. T., Yin X. M. Memory B and T cells. Annu Rev Immunol. 1991;9:193–217. doi: 10.1146/annurev.iy.09.040191.001205. [DOI] [PubMed] [Google Scholar]
  37. Wirth J. J., Carney W. P., Wheelock E. F. The effect of particle size on the immunodepressive properties of silica. J Immunol Methods. 1980;32(4):357–373. doi: 10.1016/0022-1759(80)90028-9. [DOI] [PubMed] [Google Scholar]
  38. Zoschke D. C., Skemp A. A., Defosse D. L. Lymphoproliferative responses to Borrelia burgdorferi in Lyme disease. Ann Intern Med. 1991 Feb 15;114(4):285–289. doi: 10.7326/0003-4819-114-4-285. [DOI] [PubMed] [Google Scholar]
  39. de Souza M. S., Fikrig E., Smith A. L., Flavell R. A., Barthold S. W. Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens. J Infect Dis. 1992 Mar;165(3):471–478. doi: 10.1093/infdis/165.3.471. [DOI] [PubMed] [Google Scholar]

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