Abstract
Cryptococcus neoformans is responsible for opportunistic infections in patients with cellular immune defects. However, C. neoformans-specific capsular polysaccharide antibodies have been shown to participate in host defenses during cryptococcosis. We investigated the humoral response after primary immunization in various inbred strains of mice and the genetic control. Our data strengthen the arguments for the T-independent type-2 nature of cryptococcal antigen, since CBA/N mice were unable to produce specific antibodies. They show that the influence of the genetic background is predominant for the good response with at least four independent autosomal genes governing this response, including an Igh control as reported for other polysaccharides. Immunization of intra-H-2 recombinant mice on a B10 background allowed us to identify a major histocompatibility complex control located in the subregion E α. The genetic control of antibody production following immunization with cryptococcal polysaccharide might explain the high variability of humoral responses during cryptococcosis.
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Baker, P. J., Stashak, P. W., Amsbaugh, D. F., and Prescott, B.: Characterization of the antibody response to type III pneumococcal polysaccharide at the cellular level. I. Dose-response studies and the effect of prior immunization on the magnitude of the antibody response. Immunology 20: 469–480, 1971a
Baker, P. J., Stashak, P. W., Amsbaugh, D. F., and Prescott, B.: Characterization of the antibody response to type III pneumococcal polysaccharide at the cellular level. II. Studies on the relative rate of antibody synthesis and release by antibody-producing cells. Immunology 20: 481–492, 1971b
Baker, P. J., Amsbaugh, D. F., Prescott, B., and Stashak, P. W.: Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. III. Analysis of genes governing the expression of regulatory T cell activity. J Immunogenet 3: 275–286, 1976
Baker, P. J., Rudbach, J. A., Prescott, B., Caldes, G., Evans, C., and Stashak, P. W.: Influence of multiple genes on the magnitude of the antibody response to bacterial polysaccharide antigens. Infect Immun 45: 56–61, 1984
Baker, P. J., Bailey, D. W., Fauntleroy, M. B., Stashak, P. W., Caldes, G., and Prescott, B.: Genes on different chromosomes influence the antibody response to bacterial antigens. Immunogenetics 22: 269–276, 1985
Benacerraf, B. and McDevitt, H. O.: Histocompatibility-linked immune response genes. Science 175: 273–279, 1972
Bindschadler, D. D. and Bennett, J. E.: Serology of human cryptococcosis. Ann Intern Med 69: 45–52, 1968
Biozzi, G., Stiffel, C., Mouton, D., Liacopoulos-Briot, M., Decreusefond, C., and Bouthillier, Y.: Etude du phénomène de l'immuno-cyto-adhérence au cours de l'immunisation. Ann Just Pasteur 110: 7–32, 1966
Brackertz, D., Mitchell, G. F., Vadas, M. A., Mackay, I. R., and Miller, J. F. A. P.: Studies on antigen-induced arthritis in mice. II. Immunologic correlates of arthritis susceptibility in mice. J Immunol 118: 1639–1644, 1977
Braley-Mullen, H.: Regulation of the antibody response to type III pneumococcal polysaccharide by contrasuppressor T cells. J Exp Med 160: 42–54, 1984
Breen, J. F., Lee, I. C., Vogel, F. R., and Friedman, H.: Cryptococcal capsular polysaccharide-induced modulation of murine immune responses. Infect Immun 36: 47–51, 1982
Cannat, A., Feingold, N., Caffin, J. C., and Serre, A.: Studies on the genetic control of murine humoral response to immunization with a peptidoglycan-containing fraction extracted from Brucella melitensis. Ann Immunol 130C: 675–685, 1979
Cauley, L. K. and Murphy, J. W.: Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect Immun 23: 644–651, 1979
Cherniak, R., Reiss, E., Slodki, M. E., Plattner, R. D., and Blumer, S. O.: Structure and antigenic activity of the capsular polysaccharide of Cryptococcus neoformans serotype A. Mol Immunol 17: 1025–1032, 1980
Diamond, R. D.: Antibody-dependent killing of Cryptococcus neoformans by human peripheral blood mononuclear cells. Nature 247: 148–150, 1974
Diamond, R. D. and Bennett, J. E.: Prognostic factors in Crypococcal meningitis. A study in 111 cases. Ann Intern Med 80: 176–181, 1974
Dromer, F., Charreire, J., Contrepois, A., Carbon, C., and Yeni, P.: Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun 55: 749–752, 1987a
Dromer, F., Salamero, J., Contrepois, A., Carbon, C., and Yeni, P.: Production, characterization and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide. Infect Immun 55: 742–748, 1987b
Dykstra, M. A. and Friedman, L.: Pathogenesis, lethality, and immunizing effect of experimental cutaneous cryptococcosis. Infect Immun 20: 446–455, 1978
Falconer, D. S.: Introduction à la Génétique Quantitative, p. 169, Paris, 1974
Fernandez, C., Lieberman, R., and Möller, G.: The immune response to the alpha 1–6 epitope of dextran is determined by a gene linked to the IgCH locus. Scand J Immunol 10: 77–80, 1979
Goren, M. B. and Middlebrook, G. M.: Protein conjugates of polysaccharide from Cryptococcus neoformans. J Immunol 98: 901–913, 1967
Graybill, J. R., Mitchell, L., and Drutz, D. J.: Host defense in cryptococcosis. III. Protection of nude mice by thymus transplantation. J Infect Dis 140: 546–552, 1979
Gupta, S., Ellis, M., Cesario, T., Ruhling, M., and Vayuvegula, B.: Disseminated cryptococcal infection in a patient with hypogammaglobulinemia and normal T cell functions. Ann J Med 82: 129–131, 1987
Henderson, D. K., Bennett, J. E., and Huber, M. A.: Long-lastings, specific immunologic unresponsiveness associated with cryptococcal meningitis. J Clin Invest 69: 1185–1190, 1982
Hillstrom, L. M. and Niederhuber, J. E.: Ir gene regulation of the response to trinitrophenyl-polysaccharides. Two independent genes are required for antibody production. J Exp Med 157: 2002–2016, 1983
Ivars, F., Holmberg, D., and Coutinho, A.: The immune response to bacterial dextrans. I. Genetic control of responsiveness. Scand J Immunol 17: 419–428, 1983
Jones, J. M., Amsbaugh, D. F., and Prescott, B.: Kinetics of the antibody response to type III pneumococcal polysaccharide. II. Factors influencing the serum antibody levels after immunization with an optimally immunogenic dose of antigen. J Immunol 116: 52–64, 1976
Kozel, T. R. and Casin, J., Jr.: Induction of humoral antibody response by soluble polysaccharide to Cryptococcus neoformans. Mycopathol Mycol Appl 54: 21–30, 1974
Kozel, T. R. and Follette, J. L.: Opsonization of encapsulated Cryptococcus neoformans by specific anticapsular antibody. Infect Immun 31: 978–984, 1981
Kozel, T. R., Gulley, W. F., and Cazin, J., Jr.: Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness. Infect Immun 18: 701–707, 1977
Kozel, T. R., Highison, B., and Stratton, C. J.: Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils. Infect Immun 43: 574–579, 1984
Le Moal, M. A., Colle, J. H., and Truffa-Bachi, P.: Study on B-memory generation by Tnp-Ficoll: induction but not expression is observed among various inbred mouse strains. Cell Immunol 87: 110–117, 1984
Le Moal, M. A., Guenet, J. L., and Truffa-Bachi, P.: Murine primary in vivo response to TNP-Ficoll: multigenic control involving H-2. Ann Inst Pasteur Immunol 137C: 283–298, 1986
Lewis, J. L. and Rabinovich, S.: The wide spectrum of cryptococcal infections. Am J Med 53: 315–322, 1972
Mäkelä, O., Pasanen, V. J., Sarvas, H., and Lehtonen, M.: A gene of the immunoglobulin H-chain cluster controls the murine antibody response to pneumococcal polysaccharide type 14. Scand J Immunol 12: 155–158, 1980
Miller, G. P. G. and Kohl, S.: Antibody-dependent leukocyte killing of Cryptococcus neoformans. J Immunol 131: 1455–1459, 1983
Murphy, J. W. and Cozad, G. C.: Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique. Infect Immun 5: 896–901, 1972
Nabavi, N. and Murphy, J. W.: Antibody-dependent natural killer cell-mediated growth inhibition of cryptococcus neoformans. Infect Immun 51: 556–562, 1986
Perlmutter, R. M., Hansburg, D., Briles, D. E., Nicolotti, R. A., and Davie, J. M.: Subclass restriction of murine anti-carbohydrate antibodies. J Immunol 121: 566–572, 1978
Riblet, R., Blomberg, B., Weigert, M., Lieberman, R., Taylor, B. A., and Potter, M.: Genetics of mouse antibodies. I. Linkage of the dextran response locus, VH-DEX, to allotype. Eur J Immunol 5: 775–777, 1975
Scher, I. The CBA/N mouse strain: an experimental model illustrating the influence of the X-chromosome on immunity. Adv Immunol 33: 1–71, 1982
Stein, K. E., Bona, C., Lieberman, R., Chien, C. C., and Paul, W. E.: Regulation of the anti-inulin antibody response by a nonallotype-linked gene. J Exp Med 151: 1088–1102, 1980
Taylor, C. E., Amsbaugh, D. F., Stashak, P. W., Caldes, G., Prescott, B., and Baker, P. J.: Cell surface antigens and other characteristics of T cells regulating the antibody response to type III pneumococcal polysaccharide. J Immunol 130: 19–23, 1983
Wiener, E. and Bandieri, A.: Differences in antigen handling by peritoneal macrophages from the Biozzi high and low responder lines of mice. Eur J Immunol 4: 457–463, 1974
Zuger, A., Louie, E., Holzman, R. S., Simberkoff, M. S., and Rahal, J. J.: Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment. Ann Intern Med 104: 234–240, 1986
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Dromer, F., Yeni, P. & Charreire, J. Genetic control of the humoral response to cryptococcal capsular polysaccharide in mice. Immunogenetics 28, 417–424 (1988). https://doi.org/10.1007/BF00355373
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DOI: https://doi.org/10.1007/BF00355373