Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1995 Nov;86(3):331–335.

T-cell dependent response to immune complexes abrogates B-cell unresponsiveness to pneumococcal cell wall polysaccharide.

M J Caulfield 1, D Stanko 1
PMCID: PMC1383933  PMID: 8550067

Abstract

Although > 90% of B cells from M167 (mu, kappa) immunoglobulin transgenic (Tg) mice express surface immunoglobulin that binds phosphorylcholine (PC), we found that these mice are unresponsive to immunization with pneumococcal cell wall polysaccharide (PnC), a type II thymus-independent antigen that contains PC. However, when the PnC antigen was presented as a complex with TEPC-15 or McPC-603 antibodies (which are specific for PnC), a vigorous immune response occurred in which the Tg mice produced 10-50-fold more anti-PnC antibody than when immunized with antigen alone. Interestingly, MOPC-167, which expresses the VH and VL regions used to encode the transgene antibody, was found to be a relatively poor 'carrier' for PnC, eliciting a weak anti-PnC antibody response in M167 (mu, kappa) Tg mice. In vivo administration of anti-CD4 antibody dramatically reduced the response to TEPC-15/PnC complexes, suggesting that the response is mediated by immunoglobulin (idiotype)-dependent helper T cells. The results indicate that unresponsiveness to PnC is due not to tolerance of the transgenic B cells but rather to the lack of T-cell help resulting from T-cell tolerance to the transgene-encoded idiotype.

Full text

PDF
331

Selected References

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

  1. ANDERSON H. C., McCARTY M. The occurrence in the rabbit of an acute phase protein analogous to human C reactive protein. J Exp Med. 1951 Jan;93(1):25–36. doi: 10.1084/jem.93.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caulfield M. J., Luce K. J., Proffitt M. R., Cerny J. Induction of idiotype-specific suppressor T cells with antigen/antibody complexes. J Exp Med. 1983 Jun 1;157(6):1713–1725. doi: 10.1084/jem.157.6.1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caulfield M. J., Luce K. J., Shaffer D., Lake J. P. The antibody response to specific immune complexes is under genetic control and correlates with the expression of a recurrent idiotype. J Exp Med. 1986 Jan 1;163(1):75–86. doi: 10.1084/jem.163.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caulfield M. J., Shaffer D. A computer program for the evaluation of ELISA data obtained using an automated microtiter plate absorbance reader. J Immunol Methods. 1984 Nov 30;74(2):205–215. doi: 10.1016/0022-1759(84)90288-6. [DOI] [PubMed] [Google Scholar]
  5. Cerny J., Smith J. S., Webb C., Tucker P. W. Properties of anti-idiotypic T cell lines propagated with syngeneic B lymphocytes. I. T cells bind intact idiotypes and discriminate between the somatic idiotypic variants in a manner similar to the anti-idiotopic antibodies. J Immunol. 1988 Dec 1;141(11):3718–3725. [PubMed] [Google Scholar]
  6. 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]
  7. Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
  8. Eyerman M. C., Wysocki L. T cell recognition of somatically-generated Ab diversity. J Immunol. 1994 Feb 15;152(4):1569–1577. [PubMed] [Google Scholar]
  9. Goodnow C. C., Crosbie J., Jorgensen H., Brink R. A., Basten A. Induction of self-tolerance in mature peripheral B lymphocytes. Nature. 1989 Nov 23;342(6248):385–391. doi: 10.1038/342385a0. [DOI] [PubMed] [Google Scholar]
  10. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  11. Janeway C. A., Jr, Murgita R. A., Weinbaum F. I., Asofsky R., Wigzell H. Evidence for an immunoglobulin-dependent antigen-specific helper T cell. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4582–4586. doi: 10.1073/pnas.74.10.4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jerne N. K. Idiotypic networks and other preconceived ideas. Immunol Rev. 1984 Jun;79:5–24. doi: 10.1111/j.1600-065x.1984.tb00484.x. [DOI] [PubMed] [Google Scholar]
  13. Kelsoe G., Reth M., Rajewsky K. Control of idiotope expression by monoclonal anti-idiotope and idiotope-bearing antibody. Eur J Immunol. 1981 May;11(5):418–423. doi: 10.1002/eji.1830110513. [DOI] [PubMed] [Google Scholar]
  14. Kenny J. J., Finkelman F., Macchiarini F., Kopp W. C., Storb U., Longo D. L. Alteration of the B cell surface phenotype, immune response to phosphocholine and the B cell repertoire in M167 mu plus kappa transgenic mice. J Immunol. 1989 Jun 15;142(12):4466–4474. [PubMed] [Google Scholar]
  15. Kenny J. J., Moratz C. M., Guelde G., O'Connell C. D., George J., Dell C., Penner S. J., Weber J. S., Berry J., Claflin J. L. Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance. J Exp Med. 1992 Dec 1;176(6):1637–1643. doi: 10.1084/jem.176.6.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klaus G. G. Cooperation between antigen-reactive T cells and anti-idiotypic B cells in the anti-idiotypic response to antigen-antibody complexes. Nature. 1979 Mar 22;278(5702):354–355. doi: 10.1038/278354a0. [DOI] [PubMed] [Google Scholar]
  17. Klaus G. G., Humphrey J. H., Kunkl A., Dongworth D. W. The follicular dendritic cell: its role in antigen presentation in the generation of immunological memory. Immunol Rev. 1980;53:3–28. doi: 10.1111/j.1600-065x.1980.tb01038.x. [DOI] [PubMed] [Google Scholar]
  18. Laissue J., Cottier H., Hess M. W., Stoner R. D. Early and enhanced germinal center formation and antibody responses in mice after primary stimulation with antigen-isologous antibody complexes as compared with antigen alone. J Immunol. 1971 Sep;107(3):822–831. [PubMed] [Google Scholar]
  19. Lamers M. C., Vakil M., Kearney J. F., Langhorne J., Paige C. J., Julius M. H., Mossmann H., Carsetti R., Köhler G. Immune status of a mu, kappa transgenic mouse line. Deficient response to bacterially related antigens. Eur J Immunol. 1989 Mar;19(3):459–468. doi: 10.1002/eji.1830190308. [DOI] [PubMed] [Google Scholar]
  20. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Potter M., Lieberman R. Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline. J Exp Med. 1970 Oct 1;132(4):737–751. doi: 10.1084/jem.132.4.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Sakato N., Eisen H. N. Antibodies to idiotypes of isologous immunoglobulins. J Exp Med. 1975 Jun 1;141(6):1411–1426. doi: 10.1084/jem.141.6.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith T. ACTIVE IMMUNITY PRODUCED BY SO CALLED BALANCED OR NEUTRAL MIXTURES OF DIPHTHERIA TOXIN AND ANTITOXIN. J Exp Med. 1909 Mar 1;11(2):241–256. doi: 10.1084/jem.11.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Storb U., Pinkert C., Arp B., Engler P., Gollahon K., Manz J., Brady W., Brinster R. L. Transgenic mice with mu and kappa genes encoding antiphosphorylcholine antibodies. J Exp Med. 1986 Aug 1;164(2):627–641. doi: 10.1084/jem.164.2.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TERRES G., WOLINS W. Enhanced immunological sensitization of mice by the simultaneous injection of antigen and specific antiserum. I. Effect of varying the amount of antigen used relative to the antiserum. J Immunol. 1961 Apr;86:361–368. [PubMed] [Google Scholar]
  29. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  30. Weiss S., Bogen B. MHC class II-restricted presentation of intracellular antigen. Cell. 1991 Feb 22;64(4):767–776. doi: 10.1016/0092-8674(91)90506-t. [DOI] [PubMed] [Google Scholar]
  31. Wofsy D., Seaman W. E. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985 Feb 1;161(2):378–391. doi: 10.1084/jem.161.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES