Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Jan 1;153(1):1–12. doi: 10.1084/jem.153.1.1

T cell regulation of IgG subclass antibody production in response to T- independent antigens

PMCID: PMC2186053  PMID: 6969777

Abstract

The effect of T lymphocytes on the IgM, IgG3, IgG1, IgG2b, and IgG2a responses of B lymphocytes to the type-2 T-independent antigens, trinitrophenylated (TNP)-Ficoll, and TNP-Levan, was investigated. T cell-bearing nu/+ mice were found to produce substantially higher IgG2 serum anti-TNP antibody than their athymic counterparts, and nu/nu and nu/+ IgG2a titers exhibiting more disparity than nu/nu and nu/+ IgG2b titers. The Igm, IgG3, and IgG1 anti-TNP levels in nu/nu and nu/+ mice were indistinguishable. By cell transfer experiments, it was determined that this variance in nude and heterozygote IgG2 responses could not be explained by B cell differences between the two strains or by suppressive effects on IgG2 production within nu/nu mice. Rather, the difference was shown to be the result of the absence of T cells at the time B cells were responding to antigen. In the absence of T cells, the strength of the nu/nu anti-TNP antibody response was found to be in the following order: IgM > IgG3 > IgG1 > IgG2b > IgG2a, a heirarchy identical with the recently proposed heavy chain gene order. The possibilities that T cells influence IgG2 production via their specific recognition of IgG2-bearing B cells or via signals to increase heavy chain switching of responding B cell clones are discussed.

Full Text

The Full Text of this article is available as a PDF (742.3 KB).

Selected References

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

  1. Barthold D. R., Prescott B., Stashak P. W., Amsbaugh D. F., Baker P. J. Regulation of the antibody response to type 3 pneumococcal polysaccharide. 3. Role of regulatory T cells in the development of an IgG and IgA antibody response. J Immunol. 1974 Mar;112(3):1042–1050. [PubMed] [Google Scholar]
  2. Bona C., Hooghe R., Cazenave P. A., Leguérn C., Paul W. E. Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. J Exp Med. 1979 Apr 1;149(4):815–823. doi: 10.1084/jem.149.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bottomly K., Mosier D. E. Mice whose B cells cannot produce the T15 idiotype also lack an antigen-specific helper T cell required for T15 expression. J Exp Med. 1979 Dec 1;150(6):1399–1409. doi: 10.1084/jem.150.6.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elson C. O., Heck J. A., Strober W. T-cell regulation of murine IgA synthesis. J Exp Med. 1979 Mar 1;149(3):632–643. doi: 10.1084/jem.149.3.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  6. FAHEY J. L., SELL S. THE IMMUNOGLOBULINS OF MICE. V. THE METABOLIC (CATABOLIC) PROPERTIES OF FIVE IMMUNOGLOBULIN CLASSES. J Exp Med. 1965 Jul 1;122:41–58. doi: 10.1084/jem.122.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hetzelberger D., Eichmann K. Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes. Eur J Immunol. 1978 Dec;8(12):846–852. doi: 10.1002/eji.1830081205. [DOI] [PubMed] [Google Scholar]
  9. Honjo T., Kataoka T. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc Natl Acad Sci U S A. 1978 May;75(5):2140–2144. doi: 10.1073/pnas.75.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huber B., Gershon R. K., Cantor H. Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice. J Exp Med. 1977 Jan 1;145(1):10–20. doi: 10.1084/jem.145.1.10. [DOI] [PMC free article] [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. Kishimoto T., Ishizaka K. Regulation of antibody response in vitro. VI. Carrier-specific helper cells for IgG and IgE antibody response. J Immunol. 1973 Sep;111(3):720–732. [PubMed] [Google Scholar]
  13. 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]
  14. Maki R., Traunecker A., Sakano H., Roeder W., Tonegawa S. Exon shuffling generates an immunoglobulin heavy chain gene. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2138–2142. doi: 10.1073/pnas.77.4.2138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mond J. J., Mongini P. K., Sieckmann D., Paul W. E. Role of T lymphocytes in the response to TNP-AECM-Ficoll. J Immunol. 1980 Sep;125(3):1066–1070. [PubMed] [Google Scholar]
  16. Mond J. J., Sehgal E., Sachs D. H., Paul W. E. Expression of Ia antigen on adult and neonatal B lymphocytes responsive to thymus-independent antigens. J Immunol. 1979 Oct;123(4):1619–1623. [PubMed] [Google Scholar]
  17. Mosier D. E., Zitron I. M., Mond J. J., Ahmed A., Scher I., Paul W. E. Surface immunoglobulin D as a functional receptor for a subclass of B lymphocytes. Immunol Rev. 1977;37:89–104. doi: 10.1111/j.1600-065x.1977.tb00246.x. [DOI] [PubMed] [Google Scholar]
  18. Rittenberg M. B., Amkraut A. A. Immunogenicity of trinitrophenyl-hemocyanin: production of primary and secondary anti-hapten precipitins. J Immunol. 1966 Sep;97(3):421–430. [PubMed] [Google Scholar]
  19. Roos D., Loos J. A. Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. I. Stimulation by phytohaemagglutinin. Biochim Biophys Acta. 1970 Dec 29;222(3):565–582. doi: 10.1016/0304-4165(70)90182-0. [DOI] [PubMed] [Google Scholar]
  20. Scher I., Steinberg A. D., Berning A. K., Paul W. E. X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect. J Exp Med. 1975 Sep 1;142(3):637–650. doi: 10.1084/jem.142.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schrater A. F., Goidl E. A., Thorbecke G. J., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. III. Absence in nu/nu mice: evidence for T-cell dependence of the anti-idiotypic-antibody response. J Exp Med. 1979 Oct 1;150(4):808–817. doi: 10.1084/jem.150.4.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharon R., McMaster P. R., Kask A. M., Owens J. D., Paul W. E. DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells. J Immunol. 1975 May;114(5):1585–1589. [PubMed] [Google Scholar]
  23. 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]
  24. Subbarao B., Ahmed A., Paul W. E., Scher I., Lieberman R., Mosier D. E. Lyb-7, a new B cell alloantigen controlled by genes linked to the IgCH locus. J Immunol. 1979 Jun;122(6):2279–2285. [PubMed] [Google Scholar]
  25. Wilder R. L., Yuen C. C., Subbarao B., Woods V. L., Alexander C. B., Mage R. G. Tritium (3H) radiolabeling of protein A and antibody to high specific activity: application to cell surface antigen radioimmunoassays. J Immunol Methods. 1979;28(3-4):255–266. doi: 10.1016/0022-1759(79)90192-3. [DOI] [PubMed] [Google Scholar]
  26. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]
  27. Yamashita U., Kitagawa M. Induction of anti-hapten antibody response by hapten-isologous carrier conjugate. I. Development of hapten-reactive helper cells by hapten-isologous carrier. Cell Immunol. 1974 Nov;14(2):182–192. doi: 10.1016/0008-8749(74)90204-4. [DOI] [PubMed] [Google Scholar]
  28. von Boehmer H., Shortman K. The separation of different cell classes from lymphoid organs. IX. A simple and rapid method for removal of damaged cells from lymphoid cell suspensions. J Immunol Methods. 1973 Apr;2(3):293–301. doi: 10.1016/0022-1759(73)90055-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES