Abstract
We compared the effects of adoptively transferred Th cell clones specific for the influenza hemagglutinin (HA), matrix (M), or nucleoprotein (NP) on the antibody response of nude mice infected with A/PR/8/34 influenza virus. We show that the production of antibodies to the HA absolutely requires the presence of virus-specific Th cells. Further, transfer of a Th clone specific for the internal proteins, M or NP, was as effective as was transfer of an HA-specific clone in supporting an antibody response to the HA. With each of the clones, the kinetics of the response were accelerated by approximately 3 d compared with the antibody response of normal BALB/c mice. The HA- and M- specific clones supported an isotype switch from IgM to IgG and IgA similar to that which occurs during a normal antibody response. Finally, as shown by coinfection experiments, the response required a cognate T-B interaction whether the determinants recognized by the Th and B cell are located on the same viral protein or on different viral proteins within the same virus particle. The implications of these findings for understanding the T-B interactions that occur during an effective antiviral antibody response are discussed.
Full Text
The Full Text of this article is available as a PDF (912.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anders E. M., Scalzo A. A., White D. O. Influenza viruses are T cell-independent B cell mitogens. J Virol. 1984 Jun;50(3):960–963. doi: 10.1128/jvi.50.3.960-963.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashwell J. D., DeFranco A. L., Paul W. E., Schwartz R. H. Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation. J Exp Med. 1984 Mar 1;159(3):881–905. doi: 10.1084/jem.159.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Askonas B. A., Mullbacher A., Ashman R. B. Cytotoxic T-memory cells in virus infection and the specificity of helper T cells. Immunology. 1982 Jan;45(1):79–84. [PMC free article] [PubMed] [Google Scholar]
- Brand C. M., Skehel J. J. Crystalline antigen from the influenza virus envelope. Nat New Biol. 1972 Aug 2;238(83):145–147. doi: 10.1038/newbio238145a0. [DOI] [PubMed] [Google Scholar]
- Burns W., Billups L. C., Notkins A. L. Thymus dependence of viral antigens. Nature. 1975 Aug 21;256(5519):654–656. doi: 10.1038/256654a0. [DOI] [PubMed] [Google Scholar]
- Chesnut R. W., Colon S. M., Grey H. M. Antigen presentation by normal B cells, B cell tumors, and macrophages: functional and biochemical comparison. J Immunol. 1982 Apr;128(4):1764–1768. [PubMed] [Google Scholar]
- 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]
- Ennis F. A., Wells M. A., Butchko G. M., Albrecht P. Evidence that cytotoxic T cells are part of the host's response to influenza pneumonia. J Exp Med. 1978 Nov 1;148(5):1241–1250. doi: 10.1084/jem.148.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fazekas de St Groth, Webster R. G. Disquisitions of Original Antigenic Sin. I. Evidence in man. J Exp Med. 1966 Sep 1;124(3):331–345. doi: 10.1084/jem.124.3.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerhard W., Hackett C., Melchers F. The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34. J Immunol. 1983 May;130(5):2379–2385. [PubMed] [Google Scholar]
- Germain R. N., Ashwell J. D., Lechler R. I., Margulies D. H., Nickerson K. M., Suzuki G., Tou J. Y. "Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta. Proc Natl Acad Sci U S A. 1985 May;82(9):2940–2944. doi: 10.1073/pnas.82.9.2940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glimcher L. H., Kim K. J., Green I., Paul W. E. Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells. J Exp Med. 1982 Feb 1;155(2):445–459. doi: 10.1084/jem.155.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hurwitz J. L., Hackett C. J., McAndrew E. C., Gerhard W. Murine TH response to influenza virus: recognition of hemagglutinin, neuraminidase, matrix, and nucleoproteins. J Immunol. 1985 Mar;134(3):1994–1998. [PubMed] [Google Scholar]
- Iscove N. N., Melchers F. Complete replacement of serum by albumin, transferrin, and soybean lipid in cultures of lipopolysaccharide-reactive B lymphocytes. J Exp Med. 1978 Mar 1;147(3):923–933. doi: 10.1084/jem.147.3.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Issekutz T., Chu E., Geha R. S. Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells. J Immunol. 1982 Oct;129(4):1446–1450. [PubMed] [Google Scholar]
- Kappler J., White J., Wegmann D., Mustain E., Marrack P. Antigen presentation by Ia+ B cell hybridomas to H-2-restricted T cell hybridomas. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3604–3607. doi: 10.1073/pnas.79.11.3604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kishimoto T. Factors affecting B-cell growth and differentiation. Annu Rev Immunol. 1985;3:133–157. doi: 10.1146/annurev.iy.03.040185.001025. [DOI] [PubMed] [Google Scholar]
- Lake P., Mitchison N. A. Regulatory mechanisms in the immune response to cell-surface antigens. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):589–595. doi: 10.1101/sqb.1977.041.01.068. [DOI] [PubMed] [Google Scholar]
- Lamb J. R., Woody J. N., Hartzman R. J., Eckels D. D. In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes. J Immunol. 1982 Oct;129(4):1465–1470. [PubMed] [Google Scholar]
- 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]
- Leibson H. J., Gefter M., Zlotnik A., Marrack P., Kappler J. W. Role of gamma-interferon in antibody-producing responses. 1984 Jun 28-Jul 4Nature. 309(5971):799–801. doi: 10.1038/309799a0. [DOI] [PubMed] [Google Scholar]
- Leibson H. J., Marrack P., Kappler J. W. B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor. J Exp Med. 1981 Nov 1;154(5):1681–1693. doi: 10.1084/jem.154.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malynn B. A., Wortis H. H. Role of antigen-specific B cells in the induction of SRBC-specific T cell proliferation. J Immunol. 1984 May;132(5):2253–2258. [PubMed] [Google Scholar]
- McKean D. J., Infante A. J., Nilson A., Kimoto M., Fathman C. G., Walker E., Warner N. Major histocompatibility complex-restricted antigen presentation to antigen-reactive T cells by B lymphocyte tumor cells. J Exp Med. 1981 Nov 1;154(5):1419–1431. doi: 10.1084/jem.154.5.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Melchers F., Zeuthen J., Gerhard W. Influenza virus-specific murine T cell hybridomas which recognize virus hemagglutinin in conjunction with H-2d and display helper functions for B cells. Curr Top Microbiol Immunol. 1982;100:153–163. doi: 10.1007/978-3-642-68586-6_18. [DOI] [PubMed] [Google Scholar]
- Miller J. F., Sprent J. Cell-to-cell interaction in the immune response. VI. Contribution of thymus-derived cells and antibody-forming cell precursors to immunological memory. J Exp Med. 1971 Jul 1;134(1):66–82. doi: 10.1084/jem.134.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muraguchi A., Kehrl J. H., Longo D. L., Volkman D. J., Smith K. A., Fauci A. S. Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function. J Exp Med. 1985 Jan 1;161(1):181–197. doi: 10.1084/jem.161.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakanishi K., Malek T. R., Smith K. A., Hamaoka T., Shevach E. M., Paul W. E. Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis. J Exp Med. 1984 Dec 1;160(6):1605–1621. doi: 10.1084/jem.160.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Russell S. M., Liew F. Y. Cell cooperation in antibody responses to influenza virus. I. priming of helper t cells by internal components of virion. Eur J Immunol. 1980 Oct;10(10):791–796. doi: 10.1002/eji.1830101013. [DOI] [PubMed] [Google Scholar]
- Russell S. M., Liew F. Y. T cells primed by influenza virion internal components can cooperate in the antibody response to haemagglutinin. Nature. 1979 Jul 12;280(5718):147–148. doi: 10.1038/280147a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Sullivan J. L., Mayner R. E., Barry D. W., Ennis F. A. Influenza virus infection in nude mice. J Infect Dis. 1976 Jan;133(1):91–94. doi: 10.1093/infdis/133.1.91. [DOI] [PubMed] [Google Scholar]
- Swain S. L., Dennert G., Warner J. F., Dutton R. W. Culture supernatants of a stimulated T-cell line have helper activity that acts synergistically with interleukin 2 in the response of B cells to antigen. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2517–2521. doi: 10.1073/pnas.78.4.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tony H. P., Parker D. C. Major histocompatibility complex-restricted, polyclonal B cell responses resulting from helper T cell recognition of antiimmunoglobulin presented by small B lymphocytes. J Exp Med. 1985 Jan 1;161(1):223–241. doi: 10.1084/jem.161.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Townsend A. R., Skehel J. J. Influenza A specific cytotoxic T-cell clones that do not recognize viral glycoproteins. Nature. 1982 Dec 16;300(5893):655–657. doi: 10.1038/300655a0. [DOI] [PubMed] [Google Scholar]
- Virelizier J. L., Allison A. C., Schild G. C. Immune responses to influenza virus in the mouse, and their role in control of the infection. Br Med Bull. 1979 Jan;35(1):65–68. doi: 10.1093/oxfordjournals.bmb.a071544. [DOI] [PubMed] [Google Scholar]
- Virelizier J. L. Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J Immunol. 1975 Aug;115(2):434–439. [PubMed] [Google Scholar]
- Virelizier J. L., Postlethwaite R., Schild G. C., Allison A. C. Antibody responses to antigenic determinants of influenza virus hemagglutinin. I. Thymus dependence of antibody formation and thymus independence of immunological memory. J Exp Med. 1974 Dec 1;140(6):1559–1570. doi: 10.1084/jem.140.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wortis H. H., Burkly L., Hughes D., Roschelle S., Waneck G. Lack of mature B cells in nude mice with X-linked immune deficiency. J Exp Med. 1982 Mar 1;155(3):903–913. doi: 10.1084/jem.155.3.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yap K. L., Ada G. L. Cytotoxic T cells in the lungs of mice infected with an influenza A virus. Scand J Immunol. 1978;7(1):73–80. doi: 10.1111/j.1365-3083.1978.tb00428.x. [DOI] [PubMed] [Google Scholar]
- Yap K. L., Ada G. L., McKenzie I. F. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
- Yap K. L., Ada G. L. The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes. Scand J Immunol. 1978;7(5):389–397. doi: 10.1111/j.1365-3083.1978.tb00469.x. [DOI] [PubMed] [Google Scholar]
- Yap K. L., Braciale T. J., Ada G. L. Role of T-cell function in recovery from murine influenza infection. Cell Immunol. 1979 Mar 15;43(2):341–351. doi: 10.1016/0008-8749(79)90178-3. [DOI] [PubMed] [Google Scholar]
- Yelton D. E., Desaymard C., Scharff M. D. Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981;1(1):5–11. doi: 10.1089/hyb.1.1981.1.5. [DOI] [PubMed] [Google Scholar]
- Yewdell J. W., Webster R. G., Gerhard W. U. Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule. Nature. 1979 May 17;279(5710):246–248. doi: 10.1038/279246a0. [DOI] [PubMed] [Google Scholar]
- Zamvil S., Nelson P., Trotter J., Mitchell D., Knobler R., Fritz R., Steinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. 1985 Sep 26-Oct 2Nature. 317(6035):355–358. doi: 10.1038/317355a0. [DOI] [PubMed] [Google Scholar]