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. 1986 Sep 1;164(3):841–854. doi: 10.1084/jem.164.3.841

Bystander help in primary immune responses in vivo

PMCID: PMC2188399  PMID: 2427636

Abstract

We evaluated the requirement for hapten-carrier linkage in the primary, T cell-dependent antibody response in vivo. Mice immunized with mixtures containing nonimmunogenic and immunogenic proteins developed antibody that was specific for determinants present on the nonimmunogenic carrier. Therefore, hapten-carrier linkage was not necessary for the generation of primary antibody responses. The magnitude of the bystander response was a function of the immunogenicity of the coimmunogen and the quantity of determinant- specific B cells available for activation. Interestingly, the kinetics of the bystander response, in contrast to the cognate response, were not accelerated in the presence of primed Th cells. Adoptive recipients reconstituted with primed Th cells developed accelerated cognate but not bystander antibody response, as compared with unprimed recipients. This phenomenon may reflect a regulatory mechanism invoked to limit the potentially harmful effects of nonspecific help. It was observed that while animals are tolerant to immunization with mouse (self) hemoglobin, immunization with a mixture containing mouse hemoglobin plus fowl gamma globulin resulted in the production of hemoglobin- binding autoantibodies. Thus bystander help induced by coimmunization may serve as a model for the induction of autoantibodies during normal immune responses in vivo.

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Selected References

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

  1. Asano Y., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations. J Exp Med. 1981 Oct 1;154(4):1100–1115. doi: 10.1084/jem.154.4.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bucy R. P., Kapp J. A. Ir gene control of immune responses to insulins. II. Phenotypic differences in T cell activity among nonresponder strains of mice. J Immunol. 1983 May;130(5):2062–2066. [PubMed] [Google Scholar]
  3. Calderon J., Kiely J. M., Lefko J. L., Unanue E. R. The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis. J Exp Med. 1975 Jul 1;142(1):151–164. doi: 10.1084/jem.142.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chesnut R. W., Grey H. M. Studies on the capacity of B cells to serve as antigen-presenting cells. J Immunol. 1981 Mar;126(3):1075–1079. [PubMed] [Google Scholar]
  5. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972 Jul;109(1):129–135. [PubMed] [Google Scholar]
  6. Feldmann M., Basten A. Cell interactions in the immune response in vitro. 3. Specific collaboration across a cell impermeable membrane. J Exp Med. 1972 Jul 1;136(1):49–67. doi: 10.1084/jem.136.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamaoka T., Katz D. H., Benacerraf B. Hapten-specific IgE antibody responses in mice. II. Cooperative interactions between adoptively transferred T and B lymphocytes in the development of IgE response. J Exp Med. 1973 Sep 1;138(3):538–556. doi: 10.1084/jem.138.3.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hartmann K. U. Induction of a hemolysin response in vitro. Interaction of cells of bone marrow origin and thymic origin. J Exp Med. 1970 Dec 1;132(6):1267–1278. doi: 10.1084/jem.132.6.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoffeld J. T., Marrack P., Kappler J. W. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. IV. Development of a model system demonstrating responsiveness of two T cell functions to HGG in vitro. J Immunol. 1976 Nov;117(5 PT2):1953–1959. [PubMed] [Google Scholar]
  10. Imperiale M. J., Faherty D. A., Sproviero J. F., Zauderer M. Functionally distinct helper T cells enriched under different culture conditions cooperate with different B cells. J Immunol. 1982 Nov;129(5):1843–1848. [PubMed] [Google Scholar]
  11. Jacoby R. O., Bhatt P. N., Johnson E. A., Paturzo F. X. Pathogenesis of vaccinia (IHD-T) virus infection in BALB/cAnN mice. Lab Anim Sci. 1983 Oct;33(5):435–441. [PubMed] [Google Scholar]
  12. Jensen P. E., Kapp J. A. Genetics of insulin-specific helper and suppressor T cells in nonresponder mice. J Immunol. 1985 Nov;135(5):2990–2995. [PubMed] [Google Scholar]
  13. Jensen P. E., Kapp J. A. Stimulation of helper T cells and dominant suppressor T cells that recognize autologous insulin. J Mol Cell Immunol. 1985;2(3):133–139. [PubMed] [Google Scholar]
  14. Jensen P. E., Pierce C. W., Kapp J. A. Regulatory mechanisms in immune responses to heterologous insulins. II. Suppressor T cell activation associated with nonresponsiveness in H-2b mice. J Exp Med. 1984 Oct 1;160(4):1012–1026. doi: 10.1084/jem.160.4.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kapp J. A., Strayer D. S. H-2 linked Ir gene control of antibody responses to porcine insulin. I. Development of insulin-specific antibodies in some but not all nonresponder strains injected with proinsulin. J Immunol. 1978 Sep;121(3):978–982. [PubMed] [Google Scholar]
  16. Kapp J. A., Strayer D. S., Robbins P. F., Perlmutter R. M. Insulin-specific murine antibodies of limited heterogeneity. I. Genetic control of spectrotypes. J Immunol. 1979 Jul;123(1):109–114. [PubMed] [Google Scholar]
  17. Katz D. H., Hamaoka T., Newburger P. E., Benacerraf B. Hapten-specific IgE antibody responses in mice. IV. Evidence for distinctive sensitivities of IgE and IgG B lymphocytes to the regulatory influence of T cells. J Immunol. 1974 Sep;113(3):974–983. [PubMed] [Google Scholar]
  18. Katz D. H., Paul W. E., Goidl E. A., Benacerraf B. Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization. J Exp Med. 1970 Aug 1;132(2):261–282. doi: 10.1084/jem.132.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keck K. Ir gene control of carrier recognition. III. Cooperative recognition of two or more carrier determinants on insulins of different species. Eur J Immunol. 1977 Nov;7(11):811–816. doi: 10.1002/eji.1830071113. [DOI] [PubMed] [Google Scholar]
  20. Keller D. M., Swierkosz J. E., Marrack P., Kappler J. W. Two types of functionally distinct, synergizing helper T cells. J Immunol. 1980 Mar;124(3):1350–1359. [PubMed] [Google Scholar]
  21. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  22. Marrack P. C., Kappler J. W. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. I. Evidence for their production by different T cells. J Immunol. 1975 Mar;114(3):1116–1125. [PubMed] [Google Scholar]
  23. Melchers F., Andersson J., Lernhardt W., Schreier M. H. H-2-unrestricted polyclonal maturation without replication of small B cells induced by antigen-activated T cell help factors. Eur J Immunol. 1980 Sep;10(9):679–685. doi: 10.1002/eji.1830100905. [DOI] [PubMed] [Google Scholar]
  24. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur J Immunol. 1971 Jan;1(1):10–17. doi: 10.1002/eji.1830010103. [DOI] [PubMed] [Google Scholar]
  25. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971 Jan;1(1):18–27. doi: 10.1002/eji.1830010104. [DOI] [PubMed] [Google Scholar]
  26. OVARY Z., BENACERRAF B. IMMUNOLOGICAL SPECIFICITY OF THE SECONDARY RESPONSE WITH DINITROPHENYLATED PROTEINS. Proc Soc Exp Biol Med. 1963 Oct;114:72–76. doi: 10.3181/00379727-114-28589. [DOI] [PubMed] [Google Scholar]
  27. Paul W. E., Katz D. H., Goidl E. A., Benacerraf B. Carrier function in anti-hapten immune responses. II. Specific properties of carrier cells capable of enhancing anti-hapten antibody responses. J Exp Med. 1970 Aug 1;132(2):283–299. doi: 10.1084/jem.132.2.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rajewsky K., Schirrmacher V., Nase S., Jerne N. K. The requirement of more than one antigenic determinant for immunogenicity. J Exp Med. 1969 Jun 1;129(6):1131–1143. doi: 10.1084/jem.129.6.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robbins P. F., Thomas J. W., Jensen P. E., Kapp J. A. Insulin-specific tolerance induction. I. Abrogation of helper T cell activity is controlled by H-2-linked Ir genes. J Immunol. 1984 Jan;132(1):43–49. [PubMed] [Google Scholar]
  30. Rock K. L., Benacerraf B., Abbas A. K. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J Exp Med. 1984 Oct 1;160(4):1102–1113. doi: 10.1084/jem.160.4.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rosenwasser L. J., Barcinski M. A., Schwartz R. H., Rosenthal A. S. Immune response gene control of determinant selection. II. Genetic control of the murine T lymphocyte proliferative response to insulin. J Immunol. 1979 Jul;123(1):471–476. [PubMed] [Google Scholar]
  32. Rubin A. S., Coons A. H. Specific heterologous enhancement of immune responses. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1665–1669. doi: 10.1073/pnas.68.8.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schimpl A., Wecker E., Hünig T. Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro. J Exp Med. 1977 May 1;145(5):1216–1227. doi: 10.1084/jem.145.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Singer A., Morrissey P. J., Hathcock K. S., Ahmed A., Scher I., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition. J Exp Med. 1981 Aug 1;154(2):501–516. doi: 10.1084/jem.154.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smith L. F. Amino acid sequences of insulins. Diabetes. 1972;21(2 Suppl):457–460. doi: 10.2337/diab.21.2.s457. [DOI] [PubMed] [Google Scholar]
  36. Sprent J. Role of the H-2 complex in induction of T helper cells in vivo. I. Antigen-specific selection of donor T cells to sheep erythrocytes in irradiated mice dependent upon sharing of H-2 determinants between donor and host. J Exp Med. 1978 Aug 1;148(2):478–489. doi: 10.1084/jem.148.2.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Swierkosz J. E., Marrack P., Kappler J. W. Functional analysis of T cells expressing Ia antigens. I. Demonstration of helper T-cell heterogeneity. J Exp Med. 1979 Dec 1;150(6):1293–1309. doi: 10.1084/jem.150.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tada T., Takemori T., Okumura K., Nonaka M., Tokuhisa T. Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells. J Exp Med. 1978 Feb 1;147(2):446–458. doi: 10.1084/jem.147.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Takatsu K., Tominaga A., Hamaoka T. Antigen-induced T cell-replacing factor (TRF). I. Functional characterization of a TRF-producing helper T cell subset and genetic studies on TRF production. J Immunol. 1980 May;124(5):2414–2422. [PubMed] [Google Scholar]
  40. Tees R., Schreier M. H. Selective reconstitution of nude mice with long-term cultured and cloned specific helper T cells. Nature. 1980 Feb 21;283(5749):780–781. doi: 10.1038/283780a0. [DOI] [PubMed] [Google Scholar]
  41. Waldmann H. T cell-dependent mediator in the immune response. III. The role of non-specific factor (NSF) in the in vitro immune response. Immunology. 1975 Mar;28(3):497–507. [PMC free article] [PubMed] [Google Scholar]
  42. Wolfgram L. J., Beisel K. W., Rose N. R. Heart-specific autoantibodies following murine coxsackievirus B3 myocarditis. J Exp Med. 1985 May 1;161(5):1112–1121. doi: 10.1084/jem.161.5.1112. [DOI] [PMC free article] [PubMed] [Google Scholar]

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