Abstract
In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For that reason we studied human tonsils using immunohistochemical techniques. In tissue sections from tonsils in a resting stage after recurrent tonsillitis we observed cells producing IL-1 alpha and tumour necrosis factor-alpha (TNF-alpha) which were exclusively localized in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-gamma)-producing cells was detected in the extrafollicular area, but not inside the follicles. Occasional IL-2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotypes revealed that B cells, IgM-membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells were mainly found in the mantle zones of secondary follicles. In contrast, plasma cells producing IgG1-4 and IgA1-2 were found in the extrafollicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the extrafollicular area. The co-localization of cytokine-producing cells and antibody-forming cells in human tonsil suggests that T-B cell interactions, required for B cell differentiation and isotype switching, take place in the extrafollicular area.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson U., Laskay T., Andersson J., Kiessling R., DeLey M. Phenotypic characterization of individual interferon-gamma-producing cells after OKT3 antibody activation. Eur J Immunol. 1986 Nov;16(11):1457–1460. doi: 10.1002/eji.1830161124. [DOI] [PubMed] [Google Scholar]
- Boersma W. J., Deen C., Haaijman J. J., Radl J., Claassen E. Antibodies to a short synthetic peptide related to the hinge segment of human IgG3 recognizes thermally or fixative induced conformational changes in the human IgG3 molecule. Immunology. 1989 Nov;68(3):427–430. [PMC free article] [PubMed] [Google Scholar]
- Boersma W. J., Deen C., Zegers N. D., Radl J., Haaijman J. J. IgG subclass distribution in juvenile human tonsil: IgG3 and IgG4 results of specific antibody production using synthetic peptides. Adv Exp Med Biol. 1988;237:125–132. doi: 10.1007/978-1-4684-5535-9_18. [DOI] [PubMed] [Google Scholar]
- Bowen M. B., Butch A. W., Parvin C. A., Levine A., Nahm M. H. Germinal center T cells are distinct helper-inducer T cells. Hum Immunol. 1991 May;31(1):67–75. doi: 10.1016/0198-8859(91)90050-j. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Surjan L., Jr, Berdal P. Immunoglobulin systems of human tonsils. I. Control subjects of various ages: quantification of Ig-producing cells, tonsillar morphometry and serum Ig concentrations. Clin Exp Immunol. 1978 Mar;31(3):367–381. [PMC free article] [PubMed] [Google Scholar]
- Butcher E. C., Rouse R. V., Coffman R. L., Nottenburg C. N., Hardy R. R., Weissman I. L. Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation. J Immunol. 1982 Dec;129(6):2698–2707. [PubMed] [Google Scholar]
- Claassen E., Adler L. T. Sequential double immunocytochemical staining for in situ identification of an auto-anti-allotype immune response in allotype-suppressed rabbits. J Histochem Cytochem. 1988 Dec;36(12):1455–1461. doi: 10.1177/36.12.3057069. [DOI] [PubMed] [Google Scholar]
- Del Prete G., Maggi E., Parronchi P., Chrétien I., Tiri A., Macchia D., Ricci M., Banchereau J., De Vries J., Romagnani S. IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol. 1988 Jun 15;140(12):4193–4198. [PubMed] [Google Scholar]
- Ellis J., Chain B. M., Davies D. H., Ibrahim M. A., Katz D. R., Kaye P. M., Lightstone E. Antigen presentation by dendritic cells provides optimal stimulation for the production of interleukin (IL) 2, IL 4 and interferon-gamma by allogeneic T cells. Eur J Immunol. 1991 Nov;21(11):2803–2809. doi: 10.1002/eji.1830211123. [DOI] [PubMed] [Google Scholar]
- Fernandez-Botran R., Sanders V. M., Mosmann T. R., Vitetta E. S. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med. 1988 Aug 1;168(2):543–558. doi: 10.1084/jem.168.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores-Romo L., Millsum M. J., Gillis S., Stubbs P., Sykes C., Gordon J. Immunoglobulin isotype production by cycling human B lymphocytes in response to recombinant cytokines and anti-IgM. Immunology. 1990 Mar;69(3):342–347. [PMC free article] [PubMed] [Google Scholar]
- Heinen E., Cormann N., Kinet-Denoël C. The lymph follicle: a hard nut to crack. Immunol Today. 1988 Jul-Aug;9(7-8):240–243. doi: 10.1016/0167-5699(88)91223-6. [DOI] [PubMed] [Google Scholar]
- Jelinek D. F., Splawski J. B., Lipsky P. E. The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation. Eur J Immunol. 1986 Aug;16(8):925–932. doi: 10.1002/eji.1830160809. [DOI] [PubMed] [Google Scholar]
- Kosco M. H., Gray D. Signals involved in germinal center reactions. Immunol Rev. 1992 Apr;126:63–76. doi: 10.1111/j.1600-065x.1992.tb00631.x. [DOI] [PubMed] [Google Scholar]
- Kroese F. G., Wubbena A. S., Nieuwenhuis P. Germinal centre formation and follicular antigen trapping in the spleen of lethally X-irradiated and reconstituted rats. Immunology. 1986 Jan;57(1):99–104. [PMC free article] [PubMed] [Google Scholar]
- Kuper C. F., Koornstra P. J., Hameleers D. M., Biewenga J., Spit B. J., Duijvestijn A. M., van Breda Vriesman P. J., Sminia T. The role of nasopharyngeal lymphoid tissue. Immunol Today. 1992 Jun;13(6):219–224. doi: 10.1016/0167-5699(92)90158-4. [DOI] [PubMed] [Google Scholar]
- Laman J. D., Schellekens M. M., Abacioglu Y. H., Lewis G. K., Tersmette M., Fouchier R. A., Langedijk J. P., Claassen E., Boersma W. J. Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. J Virol. 1992 Mar;66(3):1823–1831. doi: 10.1128/jvi.66.3.1823-1831.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le J., Yao J. S., Knowles D. M., 2nd, Vilcek J. Accessory function of thymic and tonsillar dendritic cells in interferon gamma production by T lymphocytes. Lymphokine Res. 1986 Summer;5(3):205–213. [PubMed] [Google Scholar]
- Leeuwenberg J. F., Van Damme J., Meager T., Jeunhomme T. M., Buurman W. A. Effects of tumor necrosis factor on the interferon-gamma-induced major histocompatibility complex class II antigen expression by human endothelial cells. Eur J Immunol. 1988 Sep;18(9):1469–1472. doi: 10.1002/eji.1830180925. [DOI] [PubMed] [Google Scholar]
- Liu Y. J., Johnson G. D., Gordon J., MacLennan I. C. Germinal centres in T-cell-dependent antibody responses. Immunol Today. 1992 Jan;13(1):17–21. doi: 10.1016/0167-5699(92)90199-H. [DOI] [PubMed] [Google Scholar]
- Miller L. C., Gray E. D., Mansour M., Abdin Z. H., Kamel R., Zaher S., Regelmann W. E. Cytokines and immunoglobulin in rheumatic heart disease: production by blood and tonsillar mononuclear cells. J Rheumatol. 1989 Nov;16(11):1436–1442. [PubMed] [Google Scholar]
- Nakagawa T., Hirano T., Nakagawa N., Yoshizaki K., Kishimoto T. Effect of recombinant IL 2 and gamma-IFN on proliferation and differentiation of human B cells. J Immunol. 1985 Feb;134(2):959–966. [PubMed] [Google Scholar]
- Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
- Quiding M., Granström G., Nordström I., Ferrua B., Holmgren J., Czerkinsky C. High frequency of spontaneous interferon-gamma-producing cells in human tonsils: role of local accessory cells and soluble factors. Clin Exp Immunol. 1993 Jan;91(1):157–163. doi: 10.1111/j.1365-2249.1993.tb03372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richtsmeier W. J. Human interferon production in tonsil and adenoid tissue cultures. Am J Otolaryngol. 1983 Sep-Oct;4(5):325–333. doi: 10.1016/s0196-0709(83)80019-2. [DOI] [PubMed] [Google Scholar]
- Rousset F., Garcia E., Banchereau J. Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J Exp Med. 1991 Mar 1;173(3):705–710. doi: 10.1084/jem.173.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruco L. P., Pisacane A., Pomponi D., Stoppacciaro A., Pescarmona E., Rendina E. A., Santoni A., Boraschi D., Tagliabue A., Uccini S. Macrophages and interdigitating reticulum cells in normal human thymus and thymomas: immunoreactivity for interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha. Histopathology. 1990 Oct;17(4):291–299. doi: 10.1111/j.1365-2559.1990.tb00732.x. [DOI] [PubMed] [Google Scholar]
- Ruco L. P., Stoppacciaro A., Pomponi D., Boraschi D., Santoni A., Tagliabue A., Uccini S., Baroni C. D. Immunoreactivity for IL-1 beta and TNF alpha in human lymphoid and nonlymphoid tissues. Am J Pathol. 1989 Nov;135(5):889–897. [PMC free article] [PubMed] [Google Scholar]
- Secrist H., Holers V. M., Levine A., Egan M., Nahm M. H., Butch A. W., Peters M. Induction of IL-4 and IL-6 synthesis in vitro: variation in signaling requirements and kinetics are dependent on the anatomic source of the responding mononuclear cells. Reg Immunol. 1990;3(6):341–348. [PubMed] [Google Scholar]
- Sung S. S., Jung L. K., Walters J. A., Chen W., Wang C. Y., Fu S. M. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. J Exp Med. 1988 Nov 1;168(5):1539–1551. doi: 10.1084/jem.168.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van den Eertwegh A. J., Boersma W. J., Claassen E. Immunological functions and in vivo cell-cell interactions of T cells in the spleen. Crit Rev Immunol. 1992;11(6):337–380. [PubMed] [Google Scholar]
- Van der Meide P. H., Dubbeld M., Schellekens H. Monoclonal antibodies to human immune interferon and their use in a sensitive solid-phase ELISA. J Immunol Methods. 1985 May 23;79(2):293–305. doi: 10.1016/0022-1759(85)90109-7. [DOI] [PubMed] [Google Scholar]
- Vitetta E. S., Fernandez-Botran R., Myers C. D., Sanders V. M. Cellular interactions in the humoral immune response. Adv Immunol. 1989;45:1–105. doi: 10.1016/s0065-2776(08)60692-6. [DOI] [PubMed] [Google Scholar]
- Zegers N. D., Claassen E., Neelen C., Mulder E., van Laar J. H., Voorhorst M. M., Berrevoets C. A., Brinkmann A. O., van der Kwast T. H., Ruizeveld de Winter J. A. Epitope prediction and confirmation for the human androgen receptor: generation of monoclonal antibodies for multi-assay performance following the synthetic peptide strategy. Biochim Biophys Acta. 1991 Jan 23;1073(1):23–32. doi: 10.1016/0304-4165(91)90178-j. [DOI] [PubMed] [Google Scholar]
- van den Eertwegh A. J., Fasbender M. J., Schellekens M. M., van Oudenaren A., Boersma W. J., Claassen E. In vivo kinetics and characterization of IFN-gamma-producing cells during a thymus-independent immune response. J Immunol. 1991 Jul 15;147(2):439–446. [PubMed] [Google Scholar]

