Abstract
The origin of the term polyclonal activation as applied to lymphocytes can be ascribed to the original finding of Nowell,1 who was the first to show that the proliferation of human peripheral blood lymphocytes in culture could be stimulated by a plant lectin phytohemagglutinin (PHA). With the development of an adequate culture system for mouse lymphocytes came an expansion of the use of this mitogen and the discovery of others, many of which are bacterial products. The value of these substances derived from the fact that lymphoid cells were stimulated non- specifically. Consequently, large numbers of cells were activated that permitted examination of the biochemical and immunologic events attendant to this process that was difficult at best to measure when dealing with a cell system based on specific antigenic recognition.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Nowell, P. C., 1960, Phytohemagglutinin: An initiator of mitosis in cultures of normal human leukocytes, Cancer Res. 20:462–466.
Sultzer, B. M., and Goodman, G. W., 1976, Endotoxin protein: A B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes, J. Exp. Med. 144:821–827.
Morrison, D. C., Betz, S. J., and Jacobs, D. M., 1976, Isolation of a lipid A bound polypeptide responsible for “LPS-initiated” mitogenesis of C3H/HeJ spleen cells, J. Exp. Med. 144:840–846.
Goldman, R. G., White, D., and Lieve, L., 1981, Identification of outer membrane proteins, including known lymphocyte mitogens as the endotoxin protein of Escherichia coli 0111, J. Immunol. 127: 1290–1294.
Wood, C. D., and Moller, G., 1984, Influence of RV 41.740, a glycoprotein extract from Klebsiella pneumoniae ,on the murine immune system. I. T-independent polyclonal B cell activation, J. Immunol. 132:616–621.
Bessler, W. G., Cox, M., Lex, A., Suhr, B., Weismuller, K-H., and Jury, G., 1985, Synthetic lipopeptide analogs of bacterial lipoprotein are potent polyclonal activators for murine B lymphocytes, J. Immunol. 135: 1900–1905.
Dziarski, R., 1980, Polyclonal activation of immunoglobulin secretion in B lymphocytes induced by staphylococcal peptidoglycan, J. Immunol. 15:2478–2483.
Greaves, M. F., Owen, J. J. T., and Raff, M. C., 1974, T and B lymphocytes: Origins, Properties and Roles in Immune Responses ,pp. 81–82, American Elsevier, Inc., New York.
Rocklin, R. E., MacDermott, R. P., Chess, L., Schlossman, S. F., and David, J. R., 1974, Studies on mediator production by highly purified T and B lymphocytes, J. Exp. Med. 140:1303–1316.
Mackaness, G. B., Auclair, D. J., and Lagrange, P. H., 1973, Immunopotentiation with BCG. I. Immune response to different strains and preparations, J. Natl. Cancer Inst ,51:1655–1667.
Miller, T. E., Mackaness, G. B., Lagrange, P. H., 1973, Immunopotentiation with BCG. II. Modulation of the response to sheep red blood cells, J. Natl. Cancer Inst. 51:1669–1676.
North, R. J., 1973, Importance of thymus-derived lymphocytes in cell-mediated immunity to infection. Cell Immunol. 7:166–176.
North, R. J., Mackaness, G. B., and Elliott, R. W., 1972, The histogenesis of immunologically committed lymphocytes. Cell. Immunol. 3:680–694.
Sultzer, B. M., and Nilsson, B. S., 1972, PPD-tuberculin-a B-cell mitogen, Nature New Biology (London). 240:198–200.
Nilsson, B. S., Sultzer, B. M., and Bullock, W. W., 1973, Purified protein derivative of tuberculin induces immunoglobulin production in normal mouse spleen cells, J. Exp. Med. 137:127–139.
Sultzer, B. M., Nilsson, B. S., and Kirschenbaum, D., 1977, Nonspecific stimulation of lymphocytes by tuberculin, Infect. Immun. 15:799–806.
Kreisler, J. M., and Moller, G., Effect of PPD on the specific immune response to heterologous red cells in vitro, J. Immunol. 112:151–161.
Coutinho, A., and Moller, G., 1975, Thymus-independent B-cell induction and paralysis, Adv. Immunol. 21:113–236.
Fauci, A. S., and Pratt, K. R., 1976, Activation of human B lymphocytes. I. Direct plaque-forming cell assay for the measurement of polyclonal activation and antigenic stimulation of human B-lymphocytes, J. Exp. Med ,144:674–684.
Lipsky, P. E., Rosenthal, A. S., 1976, The induction and regulation of guinea pig B-lymphocyte proliferation in vitro, J. Immunol. 117:1594–1602.
Jacobs, D. M., and Morrison, D. C., 1975, Dissociation between mitogenicity and immunogenicity of TNP-lipopolysaccharide, T-independent antigen, J. Exp. Med. 141:1453–1458.
Palmer, D. W., and Smith, R. T., 1974, Augmentation of PPD and LPS-induced T independent DNA synthesis in normal mouse spleen cells by leukocyte lysates from tuberculosis patients, Cell. Immunol 13:196–206.
Diamantstein, T., and Blitstein-Willinger, E., 1975, Relationship between biological activities of polymers. I. Immunogenicity, C3 activation, mitogenicity for B-cells and adjuvant properties, Immunology 29: 1087–1092.
Ben-Efraim, S., and Diamantstein, T., 1975, Mitogenic and adjuvant activity of a methanol extraction residue (MER) of tubercle bacilli on mouse lymphoid cells in vitro, Immunol. Commun. 4:565–577.
Berbase-De Lima, M., Wilkinson, J., Smith, G. S., and Walford, R. L., 1974, Age-related decline in thymic-independent immune function in a long-lived mouse strain, J. Gerontol. 29:261–268.
Moatamed, F., Karnovsky, M. J., and Unanue, S. R., 1975, Early cellular responses to mitogens and adjuvants in the mouse spleen, Lab Invest ,32:303–312.
Gronowicz, E., Coutinho, A., and Moller, G., 1974, Differentiation of B-cells: Sequential appearance of responsiveness to polyclonal activators, Scand. J. Immunol. 3:413– 421.
Moller, G., 1974, Effect of B-cell mitogens on lymphocyte subpopulations possessing C’3 and Fc receptors, J. Exp. Med. 139:969–982.
Kakiuchi, T., and Nariuchi, H., 1981, Responses of B cells with or without C3 receptor to polyclonal B cell activators, J. Immunol. 127:954–958.
Gronowicz, E., and Coutinho, A., 1976, Heterogeneity of B-cells: Direct evidence of selective triggering of distinct subpopulations by polyclonal activators, Scand. J. Immunol. 5:55–69.
Forman, J., and Moller, G., 1973, The effector cell in antibody-induced cell mediated immunity. Transplant. Rev. 17:108–149.
Etlinger, H. M., Hodgins, H. O., and Chiller, J. M., 1976, Evolution of the lymphoid system. I. Evidence for lymphocyte heterogeneity in rainbow trout revealed by the organ distribution of mitogenic responses, J. Immunol. 116:1547–1553.
Yoshida, T., Sonozaki, H., and Cohen, S., 1973, The production of migration inhibition by B and T cells of the guinea pig, J. Exp. Med. 138:784–797.
Johnson, A. G., 1983, Adjuvant action of bacterial endotoxins on antibody formation, in: Beneficial Effects of Endotoxins (A. Nowotny, ed.), pp. 249–253, Plenum Press, New York.
Primi, D., Hammarstrom, L., Smith, E., and Moller, G., 1977, Characterization of self-reactive B-cells by polyclonal B-cell activators, J. Exp. Med. 145:21–30.
Hammarstrom, L., Smith, E., Primi, D., and Moller, G., 1976, Induction of autoantibodies to red blood cells by polyclonal B-cell activators, Nature 263:60–61.
Izui, S., Kobayakawa, T., Zryd, M-J., Louis, J., and Lambert, P-H., 1977, Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice, J. Immunol. 119:2157–2162.
Diamantstein, T., Keppler, W., Blitstein-Willinger, E., and Ben-Efraim, S., 1976, Suppression of the primary immune response in vivo to sheep red blood cells by B-cell mitogens, Immunology 30:401–407.
Waldmann, T. A., and Broder, S., 1982, Polyclonal B-cell activators in the study of the regulation of immunoglobulin synthesis in the human system, Adv. Immunol. 32:1–63.
Nilsson, B. S., 1972, The response of lymphocytes from tuberculin-positive or negative humans to various doses of PPD-tuberculin in vitro. Cell. Immunol. 3:493– 500.
Closs, O., 1975, In vitro lymphocyte response to purified protein derivative, BCG, and Mycobacterium leprae in a population not exposed to leprosy. Infect. Immun. 11: 1163–1169.
Janicki, B. W., Aaron, S. A., Schechter, G. P., and McFarland, W., 1972, Tuberculin antigens active in human lymphocyte blastogenesis, Proc. Soc. Exp. Biol. Med. 141:809-813.
Ringden, O., Rynnel-Dagoo, B., Kunori, T., Smith, C. I. E., Hammarstrom, L., Freijd, A., and Moller, E., 1979, Induction of antibody synthesis in human B lymphocytes by different polyclonal B cell activators: Evaluation by direct and indirect PFC assays, Immunol. Rev. 45:195–218.
Hammarstrom, L., Bird, A. G., and Smith, C. I. E., 1980, Mitogenic activation of human lymphocytes: A protein A plaque assay evaluation of polyclonal B-cell activators, Scand. J. Immunol. 11: 1 -13.
Nishikawa, S-L, Hirata, T., Nagai, T., Mayumi, M., and Izumi, T., 1979, PPD-in-duced immunoglobulin production in human peripheral blood lymphocytes, J. Immunol. 122:2143–2149.
Blomgren, H., 1975, Role of B cells in the expression of human lymphocytes in vitro, Scand, J. Immunol. 4:499–510.
Soren, L., 1979, Suppressor cells induced by purified protein derivative of tuberculin (PPD): The suppression is mediated by cells that proliferate in response to stimulation with PPD, Scand. J. Immunol. 10: 171–178.
Matthews, K. P., Pow, P. M. ,and Weisberg, S. C. ,1977, Lymphocyte transformation by pollen extracts and purified protein derivative (PPD) in leukocyte cultures of normal human subjects, Cell Immunol. 32:120–134.
Sultzer, B. M., 1983, Lymphocyte activation by endotoxin and endotoxin protein: The role of the C3H/HeJ mouse, in: Beneficial Effects of Endotoxins (A. Nowotny, ed.), pp. 227–248, Plenum, New York.
Watson, J., Kelly, K., and Whitlock, C., 1980, Genetic control of endotoxin sensitivity, in: Microbiology 1980 (D. Schlessinger, ed.), American Society for Microbiology, Washington, D.C., pp. 4–10.
Stiffel, C., Liacopoulos-Briot, M., Decruesefond, C., and Lambert, F., 1977, Genetic selection of mice for quantitative responsiveness of lymphocytes to phytohemag-glutinin, Eur. J. Immunol. 7:291–297.
Amsbaugh, D. F., Hauser, C. T., Prescott, B., Stashak, P., Barthold, D. R., and Baker, P. J., 1972, Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. I. Evidence that an x-linked gene plays a decisive role in determining responsiveness, J. Exp. Med. 136:931–949.
Scher, I., Ahmed, A. ,Strong, D. M., Steinberg, A. D., and Paul, W. E., 1975, X-linked B-lymphocyte immune defect in CBA-HN mice. I. Studies of the function and composition of spleen cells, J. Exp. Med. 141:788–802.
Fidler, J. M., Morgan, E. L., and Weigle, W. O., 1980, B lymphocyte differentiation in the CBA/N mouse: A delay in maturation rather than total arrest. J. Immunol. 124:13–19.
Nariuchi, H., and Kakiuchi, T., 1981. Responses of spleen cells from mice with X-linked B-cell defect to polyclonal B-cell activators, purified protein derivative of tuberculin, and dextran sulfate, Cell. Immunol. 61:375–385.
Stejskal, V., Holm, G., and Perlmann, P., 1973, Differential cytotoxicity of activated lymphocytes and xenogeneic target cells. I. Activation by tuberculin and by Staphylococcus filtrate, Cell. Immunol. 8:71–81.
Wlodarski, K., Jakobisiak, M., Kassakowska, A. ,and Zelechowska, M., 1974, Stimulation of endogenous spleen colony formation by B-and T-lymphocyte mitogens, Folia Biologica 20:133–137.
Moroni, C., and Schumann, G., 1976, Mitogen induction of murine C-type viruses. II. Effect of B-lymphocyte mitogens, Virology 73: 17–22.
Mokyr, M. B., and Mitchell, M. S., 1975, Activation of lymphoid cells by BCG in vitro, Cell Immunol. 15:264–273.
Mitchell, M. S., Mokyr, M. B., and Kahane, I., 1975, Stimulation of lymphoid cells by components of BCG, J. Nat. Cancer Inst. 55:1337–1343.
Weiss, D. W., and Wells, A. Q., 1960, Vaccination against tuberculin with nonliving vaccine. III. Vaccination of guinea pigs with fractions of phenol-killed tubercle bacilli. Am. Rev. Respir. Dis. 82:339–357.
Bekierkunst, A., 1976, Stimulation of lymphocyte proliferation by killed mycobacteria and other bacterial species, Infect. Immun. 14:28–32.
Ben-Efraim, S., and Diamantstein, T., 1975, Mitogenic and adjuvant activity of a methanol extraction residue (MER) of tubercle bacilli on mouse lymphoid cells in vitro, Immunol. Commun. 4:565–577.
Ben-Efraim, S., Ulmer, A., Schmidt, M., and Diamantstein, T., 1976, Differences between lymphoid cell populations of guinea pigs and mice as determined by the response to mitogen in vitro, Int. Archs. Allergy Appl. Immunol. 51:117–130.
Azuma, I., Taniyama, T., Sugimura, K., Aladin, A. A., and Yamamura, Y., 1976, Mitogenicity of the cell walls of mycobacteria, nocardia, corynebacteria and anaerobic coryneforms, Jap. J. Microbil. 20:263–271.
Baker, L. A., Sharpton, T., Minden, P., and Campbell, P. A., 1976, Adjuvant and mitogenic properties of a supernatant fraction of sonically treated Mycobacterium bovis (BCG), Infect. Immun. 14:83–87.
Sultzer, B. M., 1978, Infection with Bacillus Calmette-Guérin activates murine thy-mus-independent(B) lymphocytes, J. Immunol. 120:254–261.
Meyer, E. M., Wilmsmann, K., Schlake, W., and Grundmann, E., 1979, Quantification of BCG-induced reactions of T and B areas in peripheral lymphoid organs of young adult Balb/c mice. A histomorphometrical and authoradiographical study. Path. Res. Pract. 164:127–140.
Mitchell, M. S., Kirkpatrick, D., Mokyr, M. B., and Gery, I., 1973, On the mode of action of BCG, Nature New Biology. 243:216–217.
Geffard, M., and Orbach-Arbouys, S., 1976, Enhancement of T suppressor activity in mice by high doses of BCG, Cancer Immunol. Immunother. 1:41–43.
Turcotte, R., Lafleur, L., and Labreche, M., 1978, Opposite effects of BCG on spleen and lymph node cells: Lymphocyte proliferation and immunoglobulin synthesis, Infect. Immun. 21:696–704.
Turcotte, R., 1981, Evidence for two distinct populations of suppressor cells in mitogen-induced blastogenesis, Infect. Immun. 34:315–322.
Turcotte, R., and Lemieux, S., 1982, Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis, Infect. Immun. 36:263–270.
Klimpel, G. R., 1979, Soluble factors from BCG-induced suppressor cells inhibit in vitro PFC responses but not cytotoxic responses, Cell. Immunol. 47:218–226.
Klimpel, G. R., and Henney, C. S., 1978, BCG-induced suppressor cells. I. Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro, J. Immunol. 120:563–569.
Allen, E. M., and Moore, V. L., 1979, Suppression of phytohemagglutinin and lipopolysaccharide responses in mouse spleen cells by Bacillus Calmette-Guérin, J. Reticuloendo. Soc. 26:349–356.
Collins, F. M., and Watson, S. R., 1979, Suppressor T-cells in BCG-infected mice, Infect. Immun. 25:491–496.
Damais, C., Bona, C., Chedid, L., Fleck, J., Nauciel, C., and Martin, J. P., 1975, Mitogenic effect of bacterial peptidoglycans possessing adjuvant activity, J. Immunol. 115:268–271.
Ciorbaru, R., Petit, J-F., Lederer, E., Zissman, E., Bona, C., and Chedid, L., 1976, Presence and subcellular localization of two distinct mitogenic fractions in the cells of Nocardia rubra and Nocardia opaca: Preparation of soluble mitogenic peptidoglycan fractions, Infect. Immun. 13: 1084–1090.
Azuma, I., Sugimura, K., Taniyama, T., Yamawaki, M., Yamamura, Y., Kusumoto, S., Okada, S., and Shiba, T., 1976, Adjuvant activity of mycobacterial fractions: Adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds, Infect. Immun. 14:18–27.
Igarashi, T., Okada, M., Azuma, I., Yamamura, Y., 1977, Adjuvant activity of synthetic N-acetylmuramyl-L-ananyl-D-isoglutamine and related compounds on cell-mediated cytotoxicity in syngeneic mice, Cell. Immunol. 34:270–278.
Specter, S., Friedman, H., and Chedid, L., 1977, Dissociation between the adjuvant vs mitogenic activity of a synthetic muramyl dipeptide for murine splenocytes, Proc. Soc. Exp. Biol. Med. 155:349–352.
Damais, C. ,Parant, M. ,and Chedid, L. ,1977, Nonspecific activation of murine spleen cells in vitro by a synthetic immunoadjuvant (n-acetylmuramyl-L-alanyl-D-isogluta-mine, Cell. Immunol. 34:49–56.
Goodman, G. W., and Sultzer, B. M., 1977, Mild alkaline hydrolysis of lipopolysac-charide endotoxin enhances mitogenicity for murine B cells, Infect. Immun. 17:205– 214.
Damais, C., Parant, M., Chedid, L., Lefrancier, P., and Choay, J., 1978, In vitro spleen cell responsiveness to various analogs of MDP (n-acetylmuramyl-L-alanyl-D-iso-glutamine), a synthetic immunoadjuvant, in MDP high-responder mice, Cell. Immunol. 35:173–179.
Wood, D. D., and Staruch, M. J., 1981, Control of the mitogenicity of muramyl dipeptide, Int. J. Immunopharmac. 3:31–44.
Specter, S., Cimprich, R., Friedman, H., and Chedid, L., 1978, Stimulation of an enhanced in vitro immune response by a synthetic adjuvant, muramyl dipeptide, J. Immunol. 120:487–491.
Watson, J., and Whitlock, C., 1978, Effect of a synthetic adjuvant on the induction of primary immune responses in T cell-depleted spleen cultures, J. Immunol. 121:383– 389.
Leclerc, C., Lowy, I., and Chedid, L., 1978, Influence of MDP and of some analogous synthetic glycopeptides on the in vitro mouse spleen cell viability and immune response to sheep erythrocytes, Cell, Immunol. 38:286–293.
LeclerC., C., Bourgeois, E., and Chedid, L., 1979, Enhancement by muramyl dipeptide of in vitro nude mice responses to a T-dependent antigen, Immunol. Commun. 8:55–64.
Lowy, I., Leclerc, C., and Chedid, L., 1980, Induction of antibodies directed against self and altered-self determinants by a synthetic adjuvant, muramyl dipeptide and some of its derivatives, Immunology ,39:441–450.
Saito-Taki, T. ,Tanabe, M. J., Mochizuki, H., Matsumoto, T., Nakano, M., Takada, H., Tsujimoto, M., Kotani, S., Kusumoto, S., Shiba, T. ,Yokogawa, K., and Kawata, S., 1980, Polyclonal B cell activation by cell wall preparations of Gram-positive bacteria. In vitro responses of spleen cells obtained from Balb/c, nu/nu, nu/ + , C3H/HeJ and Hybrid (CBA/Nx Balb/c) Fl mice, Microbiol. Immunol. 24:209–218.
Saito-Taki, T. ,Shinomiya, H., and Nakano, M., 1986, Mechanisms of polyclonal B cell activation by murayl dipeptide, Sixth Int. Cong. Immunol. Abst. 3:14.5.
Lowy, I. ,Leclerc, C., Bourgeois, E., and Chedid, L., 1980, Inhibition of mitogen-induced polyclonal activation by a synthetic adjuvant muramyl dipeptide (MDP), J. Immunol. 124:320–325.
Bahr, G. M., Modabber, F. Z., Morin, A. ,Terrier, M., Eyquem, A., and Chedid, L., 1984, Regulation by muramyl dipeptide (MDP) of the lymphoproliferative responses and polyclonal activation of human peripheral blood mononuclear cells, Clin. Exp. Immunol. 57:178–186.
Adam, A. ,Ciorbaru, R., Petit, J-F., and Lederer, E., 1972, Isolation and properties of a macromolecular water-soluble, immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis, Proc. Nat. Acad. Sci. 69:851–854.
Chedid, L., Parant, M., Parant, F., Gustafson, R. H., and Berger, F. M., 1972, Biological study of a nontoxic, water-soluble immunoadjuvant from mycobacterial cell walls, Proc. Nat. Acad. Sci. 69:855–858.
Modolell, M., Luckenbach, G. A. ,Parant, M., and Munder, P. G., 1974, The adjuvant activity of a mycobacterial water soluble adjuvant (WSA) in vitro, J. Immunol. 113:395– 403.
Goren, M., 1972, Mycobacterial lipids: Selected topics, Bacteriol. Rev. 36:33–64.
Saito, R., Tanaka, A., Sugiyama, K., Azuma, I., Yamamura, Y., Kato, M., and Goren, M., 1976, Adjuvant effect of cord factor, a mycobacterial lipid, Infect. Immun. 13:776– 781.
Parant, M., Audibert, F., Parant, F., Chedid, L., Soler, E., Polonsky, J. ,and Lederer, E., 1978, Nonspecific immunostimulant activities of synthetic trehalose-6, 6’-diesters (lower homologs of cord factor), Infect. Immun. 20: 12–19.
Saito, R., Nagao, S., Takamoto, M., Sugiyama, K., and Tanaka, A., 1977, Adjuvan-ticity (immunity-inducing property) of cord factor in mice and rats, Infect. Immun. 16:725–729.
Rook, G. A. W., and Stewart-Tull, D. E. S., 1976, The dissociation of adjuvant properties of mycobacterial components from mitogenicity, and from the ability to induce the release of mediators from macrophages, Immunology 31:389–396.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Plenum Press, New York
About this chapter
Cite this chapter
Sultzer, B.M. (1988). Polyclonal Lymphocyte Activation by M. tuberculosis and Its Products. In: Bendinelli, M., Friedman, H. (eds) Mycobacterium tuberculosis. Infectious Agents and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5418-5_13
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5418-5_13
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5420-8
Online ISBN: 978-1-4684-5418-5
eBook Packages: Springer Book Archive