Abstract
The discovery that T cells cooperate with B cells in the induction of antibody production marked a milestone in the study of immunology. Together with presentation of antigen by specialized antigen-presenting cells (a discovery made at around the same time), it provided the first and most important example of cooperation between different cell types of the immune system. The discovery of T-cell–B-cell cooperation enhanced our understanding of immunoregulation. In doing so, it laid the foundation for much of contemporary research in basic immunology, as well as present ideas about immunological diseases, ranging from immune deficiency to autoimmunity and allergy.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Burnet, F. M. & Fenner, F. The Production of Antibodies (Macmillan, Melbourne, 1949).
Billingham, R. E., Brent, L. & Medawar, P. B. Quantitative studies on tissue transplantation immunity. II. The origin, strength and duration of actively and adoptively acquired immunity. Proc. R. Soc. Lond. B 143, 58–80 (1954).
Mitchison, N. A. Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J. Exp. Med. 102, 157–177 (1955).
Miller, J. F. Immunological function of the thymus. Lancet 2, 748–749 (1961).
Good, R. A. et al. The role of the thymus in development of immunologic capacity in rabbits and mice. J. Exp. Med. 116, 733–796 (1962).
Roitt, I. M., Greaves, M. F., Torrigiani, G., Brostoff, J. & Playfair, J. H. The cellular basis of immunological responses. A synthesis of some current views. Lancet 2, 367–371 (1969).
Simonsen, M., Engelbreth-Holm, J., Jensen, E. & Poulsen, H. A study of the graft-versus-host reaction in transplantation to embryos, F1 hybrids, and irradiated animals. Annu. NY Acad. Sci. 73, 834–841 (1958).
Gowans, J. L., McGregor, D. D. & Cowen, D. M. Initiation of immune responses by small lymphocytes. Nature 196, 651–655 (1962).
Warner, N. L. & Szenberg, A. Effect of neonatal thymectomy on the immune response in the chicken. Nature 196, 784–785 (1962).
Warner, N. L. & Szenberg, A. Immunological reactivity of bursaless chickens in graft versus host reactions. Nature 199, 43–44 (1963).
Cooper, M. D., Peterson, R. D. & Good, R. A. Delineation of the thymic and bursal lymphoid systems in the chicken. Nature 205, 143–146 (1965).
Jerne, N. K. & Nordin, A. A. Plaque formation in agar by single antibody-producing cells. Science 140, 405 (1963).
Miller, J. F. & Mitchell, G. F. The thymus and the precursors of antigen reactive cells. Nature 216, 659–663 (1967).
Brownstone, A., Mitchison, N. A. & Pitt-Rivers, R. Chemical and serological studies with an iodine-containing synthetic immunological determinant 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) and related compounds. Immunology 10, 465–479 (1966).
Green, I., Benacerraf, B. & Stone, S. H. The effect of the amount of mycobacterial adjuvants on the immune response of strain 2, strain 13 and Hartley strain guinea pigs to DNP-PLL and DNP-GL. J. Immunol. 103, 403–412 (1969).
Hamerton, J. L., Barnes, D. W. & Loutit, J. F. Cytological identification of radiation-chimaeras. Nature 177, 452–454 (1956).
Mitchison, N. A. The colonisation of irradiated tissue by transplanted spleen cells. Br. J. Exp. Pathol. 37, 239–247 (1956).
Miller, J. F., De Burgh, P. M. & Grant, G. A. Thymus and the production of antibody-plaque-forming cells. Nature 208, 1332–1334 (1965).
Claman, H. N., Chaperon, E. A. & Triplett, R. F. Thymus-marrow cell combinations. Synergism in antibody production. Proc. Soc. Exp. Biol. Med. 122, 1167–1171 (1966).
Mitchell, G. F. & Miller, J. F. Immunological activity of thymus and thoracic-duct lymphocytes. Proc. Natl Acad. Sci. USA 59, 296–303 (1968).
Miller, J. F. & Mitchell, G. F. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J. Exp. Med. 128, 801–820 (1968).
Mitchell, G. F. & Miller, J. F. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J. Exp. Med. 128, 821–837 (1968).
Ovary, Z. & Benacerraf, B. Immunological specificity of the secondary response with dinitrophenylated proteins. Proc. Soc. Exp. Biol. Med. 114, 72–76 (1963).
Paul, W. E., Siskind, G. W. & Benacerraf, B. Studies on the effect of the carrier molecule on antihapten antibody synthesis. II. Carrier specificity of anti-2,4-dinitrophenyl-poly-l-lysine antibodies. J. Exp. Med. 123, 689–705 (1966).
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. 132, 261–282 (1970).
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. 132, 283–299 (1970).
Mitchison, N. A. in Antibodies (ed. Frisch, L.) 431–439 (Cold Spring Harbor Laboratory, Cold Spring Harbor, 1967).
Mitchison, N. A. in Organ Transplantation Today (eds Mitchison, N. A., Hattinga, G. J. & Verschure, J. C. M.) 13–23 (Excerpta Medical Foundation, Amsterdam, 1969).
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. 1, 10–17 (1971).
Mitchison, N. A. The carrier effect in the secondary response to hapten protein conjugates. II. Cellular cooperation. Eur. J. Immunol. 1, 18–27 (1971).
Raff, M. C. θ isoantigen as a marker of thymus-derived lymphocytes in mice. Nature 224, 378–379 (1969).
Raff, M. C. Role of thymus-derived lymphocytes in the secondary humoral immune response in mice. Nature 226, 1257–1258 (1970).
Niederhuber, J., Moller, E. & Makela, O. Cytotoxic effect of anti-θ and anti-mouse specific B lymphocyte antigen (MBLA) antisera on helper cells and antibody-forming cell precursors in the immune response of mice to the 4-hydroxy-3,5-dinitrophenacetyl (NNP) hapten. Eur. J. Immunol. 2, 371–374 (1972).
Rajewsky, K., Rottlander, E., Peltre, G. & Muller, B. The immune response to a hybrid protein molecule; specificity of secondary stimulation and of tolerance induction. J. Exp. Med. 126, 581–606 (1967).
Rajewsky, K., Schirrmacher, V., Nase, S. & Jerne, N. K. The requirement of more than one antigenic determinant for immunogenicity. J. Exp. Med. 129, 1131–1143 (1969).
Mitchison, N. A., Rajewsky, K. & Taylor, R. B. in Developmental Aspects of Antibody Formation and Structure (eds Sterzl, J. & Riha, I.) 547–561 (Academia, Prague, 1969).
Janeway, C. A. J., Sharrow, S. O. & Simpson, E. T-cell populations with different functions. Nature 253, 544–546 (1975).
Rosenthal, A. S. & Shevach, E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J. Exp. Med. 138, 1194–1212 (1973).
Lanzavecchia, A., Ferrarini, M. & Celada, F. Human T cell lines with antigen specificity and helper activity. Eur. J. Immunol. 12, 468–474 (1982).
Mitchison, A. Latent help to and from H–2 antigens. Eur. J. Immunol. 22, 123–127 (1992).
Huppa, J. B. & Davis, M. M. T-cell-antigen recognition and the immunological synapse. Nature Rev. Immunol. 3, 973–983 (2003).
McVernon, J., Mitchison, N. A. & Moxon, E. R. T helper cells and efficacy of Haemophilus influenzae type b conjugate vaccination. The Lancet Infect. Dis. 4, 40–44 (2004).
Acknowledgements
Thanks to H. Claman, G. Nossal, W. Paul, M. Raff, K. Rajewsky and others for critical advice.
Author information
Authors and Affiliations
Related links
Rights and permissions
About this article
Cite this article
Mitchison, N. T-cell–B-cell cooperation. Nat Rev Immunol 4, 308–312 (2004). https://doi.org/10.1038/nri1334
Issue Date:
DOI: https://doi.org/10.1038/nri1334
This article is cited by
-
Targeting Endocytosis and Cell Communications in the Tumor Immune Microenvironment
Cell Communication and Signaling (2022)
-
Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action
Nature Reviews Chemistry (2021)
-
Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes
Clinical and Translational Oncology (2021)
-
PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation
Immunogenetics (2020)
-
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
Nature (2020)