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. 1995 Dec;76(6):419–424.

In vivo and in vitro study of the primary and secondary antibody response to a bacterial antigen in aged mice.

C Borghesi 1, C Nicoletti 1
PMCID: PMC1997203  PMID: 8652362

Abstract

One of the most important manifestations of aging in both humans and laboratory animals is a gradual decline in immune effectiveness. However, it is not clear as to how general is this decline. We here report that aged BALB/c mice showed no decline in the magnitude of the in vivo primary antibody response to phosphorylcholine (PC), an immunodominant epitope of the Streptococcus pneumoniae R36a (Pn). Often it appeared that aged mice responded better than young syngeneic mice. In contrast, the secondary antibody response had a different profile, with aged mice showing a marked decrease in PC-specific antibody. Further in vitro studies were conducted in order to determine the cause of the decline of the secondary antibody response in aging. We noted that B cells from young and aged donors, either primed or twice immunized with the antigen, when cultured without T cells and in the presence of antigen did not display any significant difference in their antibody response to PC. However, L3T4 cells from aged BALB/c mice, previously immunized twice with Pn, failed to augment the in vitro B cell response as compared to L3T4 cells from young mice. Moreover, we found that Lyt 2 cells from young and aged mice had no regulatory effects on the anti-PC response in vitro. Further in vivo experiments demonstrated that alteration of the idiotypic network may not be related to a decline in the secondary antibody response since two injections of the antigen are unable to elicit an anti-idiotypic antibody response in either young or aged mice. These data demonstrate that the decline of the anti-PC response after a secondary challenge with Pn is linked to defects in the T cell compartment.

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Selected References

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  1. Brown P. B., Köhler H., Rowley D. A. Specific suppression of the antibody response in vitro by serum from paralyzed mice. J Immunol. 1975 Aug;115(2):419–424. [PubMed] [Google Scholar]
  2. Cerny J., Cronkhite R. An independent regulation of distinct idiotopes of the T15 idiotype by autologous T cells. Ann N Y Acad Sci. 1983;418:31–39. doi: 10.1111/j.1749-6632.1983.tb18052.x. [DOI] [PubMed] [Google Scholar]
  3. Cerny J., Wallich R., Hammerling G. J. Analysis of T15 idiotopes by monoclonal antibodies: variability of idiotopic expression on phosphorylcholine-specific lymphocytes from individual inbred mice. J Immunol. 1982 Apr;128(4):1885–1891. [PubMed] [Google Scholar]
  4. Cosenza H. Detection of anti-idiotype reactive cells in the response to phosphorylcholine. Eur J Immunol. 1976 Feb;6(2):114–116. doi: 10.1002/eji.1830060208. [DOI] [PubMed] [Google Scholar]
  5. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  6. Goidl E. A., Innes J. B., Weksler M. E. Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice. J Exp Med. 1976 Oct 1;144(4):1037–1048. doi: 10.1084/jem.144.4.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goidl E. A., Thorbecke G. J., Weksler M. E., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response: changes in the auto-anti-idiotypic antibody response and the idiotype repertoire associated with aging. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6788–6792. doi: 10.1073/pnas.77.11.6788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Inman J. K., Merchant B., Tacey S. E. Synthesis of large haptenic compounds having a common functional group that permits covalent linkage to proteins, cell surfaces, and adsorbents. Immunochemistry. 1973 Mar;10(3):153–163. doi: 10.1016/0019-2791(73)90004-9. [DOI] [PubMed] [Google Scholar]
  9. Kelsoe G., Isaak D., Cerny J. Thymic requirement for cyclical idiotypic and reciprocal anti-idiotypic immune responses to a T-independent antigen. J Exp Med. 1980 Feb 1;151(2):289–300. doi: 10.1084/jem.151.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Makinodan T., Perkins E. H., Chen M. G. Immunologicc activity of the aged. Adv Gerontol Res. 1971;3:171–198. [PubMed] [Google Scholar]
  11. Marcenaro L., Russo C., Kim Y. T., Siskind G. W., Weksler M. E. Immunological studies of aging. Normal B-cell repertoire in aged mice: studies at a clonal level. Cell Immunol. 1989 Mar;119(1):202–210. doi: 10.1016/0008-8749(89)90236-0. [DOI] [PubMed] [Google Scholar]
  12. Nagel J. E., Crest F. J., Adler W. H. Human B cell function in normal individuals of various ages. 1. In vitro enumeration of pokeweed-induced peripheral blood lymphocyte immunoglobulin-synthesizing cells and the comparison of the results with numbers of peripheral B and T cells, mitogen responses, and levels of serum immunoglobulins. Clin Exp Immunol. 1981 Jun;44(3):646–653. [PMC free article] [PubMed] [Google Scholar]
  13. Nicoletti C. Antibody response in aged C57BL/6 mice: T helper cells are responsible for the decline of the primary antibody response to a bacterial antigen in aging. Immunobiology. 1994 Feb;190(1-2):127–137. doi: 10.1016/S0171-2985(11)80288-3. [DOI] [PubMed] [Google Scholar]
  14. Nicoletti C., Borghesi-Nicoletti C. Detection of autologous antiidiotypic antibody-forming cells by a modified enzyme-linked immunospot (ELISPOT). Res Immunol. 1992 Nov-Dec;143(9):919–925. doi: 10.1016/0923-2494(92)80115-2. [DOI] [PubMed] [Google Scholar]
  15. Perlmutter R. M., Crews S. T., Douglas R., Sorensen G., Johnson N., Nivera N., Gearhart P. J., Hood L. The generation of diversity in phosphorylcholine-binding antibodies. Adv Immunol. 1984;35:1–37. doi: 10.1016/s0065-2776(08)60572-6. [DOI] [PubMed] [Google Scholar]
  16. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  17. Schneider E. L. Infectious diseases in the elderly. Ann Intern Med. 1983 Mar;98(3):395–400. doi: 10.7326/0003-4819-98-3-395. [DOI] [PubMed] [Google Scholar]
  18. Segre D., Segre M. Humoral immunity in aged mice. II. Increased suppressor T cell activity in immunologically deficient old mice. J Immunol. 1976 Mar;116(3):735–738. [PubMed] [Google Scholar]
  19. Seth A., Nagarkatti M., Nagarkatti P. S., Subbarao B., Udhayakumar V. Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro. Mech Ageing Dev. 1990 Mar 15;52(2-3):107–124. doi: 10.1016/0047-6374(90)90118-y. [DOI] [PubMed] [Google Scholar]
  20. Szewczuk M. R., Campbell R. J. Loss of immune competence with age may be due to auto-anti-idiotypic antibody regulation. Nature. 1980 Jul 10;286(5769):164–166. doi: 10.1038/286164a0. [DOI] [PubMed] [Google Scholar]
  21. Wade A. W., Szewczuk M. R. Aging, idiotype repertoire shifts, and compartmentalization of the mucosal-associated lymphoid system. Adv Immunol. 1984;36:143–188. doi: 10.1016/s0065-2776(08)60901-3. [DOI] [PubMed] [Google Scholar]
  22. Zharhary D., Klinman N. R. A selective increase in the generation of phosphorylcholine-specific B cells associated with aging. J Immunol. 1986 Jan;136(2):368–370. [PubMed] [Google Scholar]
  23. Zharhary D., Klinman N. R. Antigen responsiveness of the mature and generative B cell populations of aged mice. J Exp Med. 1983 Apr 1;157(4):1300–1308. doi: 10.1084/jem.157.4.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zharhary D., Klinman N. R. B cell repertoire diversity to PR8 influenza virus does not decrease with age. J Immunol. 1984 Nov;133(5):2285–2287. [PubMed] [Google Scholar]

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