The Significance of Hereditary Asplenia for Immunologic Competence

  • Wanda Lizak Welles
  • Jack R. Battisto


Immunologic integrity results from a finely controlled balance of the cellular and molecular mechanisms that provide for surveillance, tolerance, and immunologic response. In recent years, as knowledge of these mechanisms has evolved, the spleen has emerged as an important regulatory organ that exerts myriad influences upon lymphocytes in situ as well as in other immunologic domains. This chapter, in addition to presenting a comprehensive view of splenic immunologic capability, will also focus on the concept that the spleen is influential to the maturation and function of lymphocytes within other immunologic sites (Battisto et al, 1971; Welles and Battisto, 1978, 1979). Both of these objectives will be achieved by examining studies of the hereditarily asplenic mouse, which provides a unique vehicle for the evaluation of splenic influences upon immunologic function.


Spleen Cell Newcastle Disease Virus Suppressor Cell Thymus Cell Antibody Synthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Argyris, B. F., 1978, Suppressor activity in the spleen of neonatal mice, Cell. Immunol. 36: 354.PubMedCrossRefGoogle Scholar
  2. Auerbach, R., 1978, Ontogeny of immune responsiveness in the absence of the spleen: A review, Dev. Comp. Immunol. 2: 219.PubMedCrossRefGoogle Scholar
  3. Barnett, J. B., and Wust, C. J., 1978, Levels of homocytotropic antibody in hereditarily asplenic, splenecto-mized and normal mice, Int. Arch. Allergy Appl. Immunol. 56: 558.PubMedCrossRefGoogle Scholar
  4. Bassett, M., Coons, T. A., Wallis, W., Goldberg, E., and Williams, R. C., Jr., 1977, Suppression of stimulation in mixed leukocyte culture by newborn splenic lymphocytes in the mouse, J. Immunol. 119: 1855.PubMedGoogle Scholar
  5. Basten, A., Miller, J. F. A. P., Sprent, J., and Cheers, C., 1974, Cell-to-cell interaction in the immune response. X. T-cell dependent suppression in tolerant mice, J. Exp. Med. 140: 199.PubMedCrossRefGoogle Scholar
  6. Battisto, J. R., Cantor, L. C., Borek, F., Goldstein, A. L., and Cabrerra, E., 1969, Immunoglobulin synthesis in hereditarily spleenless mice, Nature (London) 222: 1196.CrossRefGoogle Scholar
  7. Battisto, J. R., Borek, F., and Bucsi, R. A., 1971, Splenic determination of immunocompetence: Influence on other lymphoid organs, Cell. Immunol. 2: 627.PubMedCrossRefGoogle Scholar
  8. Battisto, J. R., Finke, J. H., and Yen, B., 1979, Correlation of B cell acquisition of differentiation antigens with capacity to interact with allogeneic effect factor (AEF), in: Macrophages and Lymphocytes: Nature, Functions and Interactions (M. R. Escobar and H Friedman, eds.), pp. 229–238, Plenum Press, New York.Google Scholar
  9. Berryman, P. L., and Silvers, W. K., 1979, Failure to confirm the influence of splenectomy on the survival of H-Y-incompatible skin grafts in mice, Transplantation 27: 287.PubMedCrossRefGoogle Scholar
  10. Borecky, L., and Lackovic, V., 1967, The cellular background of interferon production in vivo, Acta Virol. 11: 150.Google Scholar
  11. Borek, F., 1976, Distribution of sheep red blood cells in tissues of normal and hereditarily spleenless mice, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 435–437, Elsevier/North-Holland, Amsterdam.Google Scholar
  12. Borek, F., Battisto, J. R., and Fabian, D., 1969, Distribution of sheep red blood cells in tissues of normal and hereditarily spleenless mice, Fed. Proc. Fed. Am. Soc. Exp. Biol. 28: 432 (abstract).Google Scholar
  13. Bowdler, A. J., 1976, The role of the spleen and splenectomy in autoimmune hemolytic disease, Semin. Hematol. 13: 335.PubMedGoogle Scholar
  14. Bucsi, R. A., and Battisto, J. R., 1973, Splenic imprint on lymphoid cells, Exp. Hematol. 1: 72 (abstract).Google Scholar
  15. Bucsi, R. A., Borek, F., and Battisto, J. R., 1972, Splenic replenishment of synergistic ability to bone marrow and thymus cells of neonatally splenectomized CBA mice, J. Exp. Med. 136: 761.PubMedCrossRefGoogle Scholar
  16. Chanana, A. D., Joel, D. D., Schaedeli, J., Hess, M. W., and Cottier, H., 1973, Thymus cell migration: 3HTdR-labeled and theta-positive cells in peripheral lymphoid tissues of newborn mice, Adv. Exp. Med. Biol. 29: 79.PubMedGoogle Scholar
  17. Claret, I., Morales, L., and Montaner, A., 1975, Immunological studies in the post-splenectomy syndrome, J. Pediatr. Surg. 10: 59.PubMedCrossRefGoogle Scholar
  18. Constantopoulos, A., Najjar, V. A., Wish, J. B., Necheles, T. H., and Stolbach, L. L., 1973, Defective phagocytosis due to tuftsin deficiency in splenectomized subjects, Am. J. Dis. Child. 125: 663.PubMedGoogle Scholar
  19. Coons, T. A., and Goldberg, E. H., 1978, Rejection of male skin grafts by splenectomized female mice, Science 200: 320.PubMedCrossRefGoogle Scholar
  20. Fabri, P. J., Metz, E. N., Nick, W. V., and Zollinger, R. M., 1974, A quarter century with splenectomy, Arch. Surg. 108: 569.PubMedCrossRefGoogle Scholar
  21. Fahey, J. L., and Barth, W. F., 1965, The immunoglobulins of mice. 4. Serum immunoglobulin changes following birth, Proc. Soc. Exp. Biol. Med. 118: 596.PubMedGoogle Scholar
  22. Farrar, W. L., and Elgert, K. D., 1978, Suppressor cell activity in tumor-bearing mice. II. Inhibition of DNA synthesis and DNA polymerases by TBH splenic suppressor cells, J. Immunol. 120: 1354.PubMedGoogle Scholar
  23. Feldman, J. D., 1972, Immunological enhancement: A study of blocking antibodies, Adv. Immunol. 15: 167.PubMedCrossRefGoogle Scholar
  24. Fightlin, R. S., Lytton, B., and Gershon, R. K., 1975, Splenic regulation of lymphocyte trapping in lymph nodes draining tumor grafts, J. Immunol. 115: 345.PubMedGoogle Scholar
  25. Finke, J. H., and Battisto, J. R., 1976, Maturational requirements of murine differentiation antigens 1 and 2 that are operative in isogeneic lymphocyte interactions, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 89–103, Elsevier/North-Holland, Amsterdam.Google Scholar
  26. Fiocchi, C., 1976, Quantitation of immunoglobulins in hereditarily asplenic mice, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 427–434, Elsevier/North-Holland, Amsterdam.Google Scholar
  27. Fletcher, M. P., Ikeda, R. M., and Gershwin, M. E., 1976, Oncogenesis in congenitally asplenic mice, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 377–389, Elsevier/North-Holland, Amsterdam.Google Scholar
  28. Fletcher, M. P., Ikeda, R. M., and Gershwin, M. E., 1977, Splenic influence of T cell function: The immu-nobiology of the inbred hereditarily asplenic mouse, J. Immunol. 119: 110.PubMedGoogle Scholar
  29. Fruitstone, M. J., Michaels, B. S., Rudloff, D. A. C., and Sigel, M. M., 1966, Role of the spleen in interferon production in mice, Proc. Soc. Exp. Biol. Med. 122: 1008.PubMedGoogle Scholar
  30. Garcia-Giralt, E., Morales, V. H., Bizzini, B., and Lasalvia, E., 1973, Prevention of graft versus host reaction by incubation of lymphoid cells with a splenic extract (not affecting the repopulation of the haemopoietic tissue), Cell Tissue Kinet. 6: 567.PubMedGoogle Scholar
  31. Gershon, R. K., 1974, T-cell control of antibody production, Contemp. Top. Immunobiol. 3: 1.PubMedCrossRefGoogle Scholar
  32. Gershon, R. K., 1975, A disquisition on suppressor T cells, Transplant. Rev. 26: 170.PubMedGoogle Scholar
  33. Gershon, R. K., Lance, E. M., and Kondo, K., 1974, Immuno-regulatory role of spleen localizing thymocytes, J. Immunol. 112: 546.PubMedGoogle Scholar
  34. Gershwin, M. E., Castles, J. J., Ikeda, R. M., Erickson, K., and Montero, J., 1979, Studies of congenitally immunologic mutant New Zealand mice. I. Autoimmune features of hereditarily asplenic (Dh/+) NZB mice; reduction of naturally occurring thymocytotoxic antibody and normal suppressor function, J. Immunol. 122: 710.PubMedGoogle Scholar
  35. Glaser, M., 1979, Augmentation of specific immune response against syngeneic SV40-induced tumor-associated antigens by splenectomy, Cell. Immunol. 45: 230.PubMedCrossRefGoogle Scholar
  36. Green, M. C., 1967, A defect of the splanchnic mesoderm caused by the mutant gene dominant hemimelia in the mouse, Dev. Biol. 15: 62.PubMedCrossRefGoogle Scholar
  37. Gutman, N. R., and Sorokin, A. M., 1973, The effect of splenectomy and anti-lymphocytic serum upon interferon and antibody production, Vopr. Virusol. 1: 73.Google Scholar
  38. Haaijman, J. J., Schuit, H. R. E., and Hijmans, W., 1977, Immunoglobulin-containing cells in different lymphoid organs of the CBA mouse during its lifespan, Immunology 32: 427.PubMedGoogle Scholar
  39. Hancock, B. W., Bruce, L., Ward, A. M., and Richmond, J., 1977, The immediate effects of splenectomy, radiotherapy and intensive chemotherapy on the immune status of patients with malignant lymphoma, Clin. Oncol. 3: 137.PubMedGoogle Scholar
  40. Howe, M. L., Goldstein, A. L., and Battisto, J. R., 1970, Isogeneic lymphocyte interaction: Recognition of self-antigens by cells of the neonatal thymus, Proc. Natl. Acad. Sci. USA 67: 613.PubMedCrossRefGoogle Scholar
  41. Howie, J. B., and Helyer, B. J., 1968, The immunology and pathology of NZB mice, Adv. Immunol. 9: 215.PubMedCrossRefGoogle Scholar
  42. Ito, Y., Kunii, A., Mori, N., and Nagata, I., 1971, Effects of splenectomy on production of endotoxin-type interferon in mice, Virology 44: 638.PubMedCrossRefGoogle Scholar
  43. Johnson, L. L, 1978, Tail skin grafts do not show accelerated rejection on splenectomized hosts, Immunoge-netics 6: 483.CrossRefGoogle Scholar
  44. Kalpaktsoglou, P. K., and Good, R. A., 1973, Mortality and five classes of mouse immunoglobulins in early splenectomy, Int. Arch. Allergy Appl. Immunol. 44: 697.PubMedCrossRefGoogle Scholar
  45. Kirchner, H., Holden, H. T., and Herberman, R. B., 1975, Splenic suppressor macrophages induced in mice by injection of Corynebacterium parvum, J. Immunol. 115: 1212.PubMedGoogle Scholar
  46. Lair, S. V., Braun, A., and Lozzio, B. B., 1974, Induction of interferon in hereditarily asplenic mice with and without a neonatal spleen cell transplant, Proc. Soc. Exp. Biol. Med. 146: 475.PubMedGoogle Scholar
  47. Landahl, C. A., Chakravarty, A., Sulman, M., Kubai, L., and Auerbach, R., 1976, Studies on the maturation of immune responsiveness in the mouse. II. Role of the spleen, J. Immunol. 117: 151.PubMedGoogle Scholar
  48. Lappe, M., and Shalk, J., 1971, Necessity of the spleen for balanced secondary sex ratios following maternal immunization with male antigen, Transplantation 11: 491.PubMedCrossRefGoogle Scholar
  49. Lozzio, B. B., 1972, Hematopoiesis in congenitally asplenic mice, Am. J. Physiol. 222: 290.PubMedGoogle Scholar
  50. Lozzio, B. B., and Wargon, L. B., 1974, Immune competence of hereditarily asplenic mice, Immunology 27: 167.PubMedGoogle Scholar
  51. Lozzio, B. B., Lopez, D. M., Coulson, P., and Lair, S. V., 1979, High incidence of mammary tumors in mice with inherited asplenia carriers for the nude gene, Cancer Res. 39: 1529.PubMedGoogle Scholar
  52. Lynn, H. B., 1976, A re-evaluation of splenectomy, Pediatr. Ann. 5: 12.PubMedGoogle Scholar
  53. McCullagh, P., 1976, Suppressor cells in homograft tolerant rats, Aust. J. Exp. Biol. Med. Sci. 53: 431.PubMedGoogle Scholar
  54. Machado, E. A., and Lozzio, B. B., 1976, Hyposplenia, asplenia and immunodeficiency, Am. J. Pathol. 85: 515.PubMedGoogle Scholar
  55. Meier, H., and Hoag, W. G., 1962, Blood proteins and immune response in mice with hereditary absence of spleen, Naturwissenschaften 49: 329.CrossRefGoogle Scholar
  56. Milas, L., and Mujagic, H., 1973, The effect of splenectomy on fibrosarcoma “metastases” in lungs of mice, Int. J. Cancer 11: 186.PubMedCrossRefGoogle Scholar
  57. Mosier, D. E., and Johnson, B. M., 1975, Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes, J. Exp. Med. 141: 216.PubMedCrossRefGoogle Scholar
  58. Nishioka, K., Constantopoulos, A., Satoh, P. S., and Najjar, V. A., 1972, The characteristics, isolation and synthesis of the phagocytosis stimulating peptide tuftsin, Biochem. Biophys. Res. Commun. 47: 172.PubMedCrossRefGoogle Scholar
  59. Nordlund, J. J., and Gershon, R. K., 1975, Splenic regulation of the clinical appearance of small tumors, J. Immunol. 114: 1486.PubMedGoogle Scholar
  60. Nossal, G. J. V., and Pike, B. L., 1973, Differentiation of B lymphocytes from stem cell precursors, Adv. Exp. Med. Biol. 29: 11.PubMedGoogle Scholar
  61. Pierce, C. W., and Kapp, J. A., 1976, Regulation of immune responses by suppressor T cells, Contemp. Top. Immunobiol. 5: 91.Google Scholar
  62. Ponzio, N. M., Finke, J. H., and Battisto, J. R., 1975, Adult murine lymph node cells respond blastogenically to a new differentiation antigen on isologous and autologous B lymphocytes, J. Immunol. 114: 971.PubMedGoogle Scholar
  63. Rabinowitz, S. G., 1976, Measurement and comparison of the proliferative and antibody responses of neonatal, immature and adult murine spleen cells to T-dependent and T-independent antigens, Cell. Immunol. 21: 201.PubMedCrossRefGoogle Scholar
  64. Rieger, M., and Hilgert, I., 1977, The involvement of a suppressor mechanism in neonatally induced allograft tolerance in mice, J. Immunogenet. 4: 61.PubMedCrossRefGoogle Scholar
  65. Romball, C. G., and Weigle, W. O., 1977, Splenic role in the regulation of immune responses, Cell. Immunol. 34: 376.PubMedCrossRefGoogle Scholar
  66. Roubinian, J. R., Papoian, R., Pillarisetty, R., Sawada, S., and Talal, N., 1977, Immunological regulation of spontaneous antibodies to DNA and RNA. III. Early effects of neonatal thymectomy and splenectomy, Immunology 33: 399.PubMedGoogle Scholar
  67. Rozing, J., Brons, N. H. C., and Bener, R. 1978, Effects of splenectomy on the humoral immune system. A study in neonatally and adult splenectomized mice, Immunology 34: 909.PubMedGoogle Scholar
  68. Russell, J. L., and Golub, E. S., 1977, Functional development of the interacting cells in the immune response. III. Role of the neonatal spleen, Eur. J. Immunol. 7: 305.PubMedCrossRefGoogle Scholar
  69. Searle, A. G., 1959, Hereditary absence of spleen in the mouse, Nature (London) 184: 1419.CrossRefGoogle Scholar
  70. Searle, A. G., 1964, The genetics and morphology of two “luxoid” mutants in the house mouse, Genet. Res. 5: 171.CrossRefGoogle Scholar
  71. Shillcock, J. A., Pappas, F., and Battisto, J. R., 1973, Effect of neonatal splenectomy on cellular cooperation in IgM and IgG synthesis, Fed. Proc. Fed. Am. Soc. Exp. Biol. 32: 966 (abstract).Google Scholar
  72. Spear, P. G., and Edelman, G. M., 1974, Maturation of the humoral immune response in mice, J. Exp. Med. 139: 249.PubMedCrossRefGoogle Scholar
  73. Spear, P. G., Wang, A., Rutishauser, V., and Edelman, G. M., 1973, Characterization of splenic lymphoid cells in fetal and newborn mice, J. Exp. Med. 138: 557.PubMedCrossRefGoogle Scholar
  74. Streilein, J. W., and Wiesner, J., 1977, Influence of splenectomy on first set reactions of C57BL/6 females to male skin isografts, J. Exp. Med. 146: 809.PubMedCrossRefGoogle Scholar
  75. Sy, M., Miller, S. D., Kowach, H. B., and Claman, H. N., 1977, A splenic requirement for the generation of suppressor T cells, J. Immunol. 119: 2095.PubMedGoogle Scholar
  76. Tada, T., Taniguchi, M., and Takemori, T., 1975, Properties of primed suppressor T cells and their products, Transplant. Rev. 26: 106.PubMedGoogle Scholar
  77. Talal, N., 1976, Disordered immunologic regulation and autoimmunity, Transplant. Rev. 31: 240.PubMedGoogle Scholar
  78. Tsukui, K., 1977, Influenza virus-induced interferon production in mouse spleen cell culture: T cells as the main producer, Cell. Immunol. 32: 243.PubMedCrossRefGoogle Scholar
  79. Waldman, J. D., Rosenthal, A., Smith, A. L., Shurin, S., and Nadas, A. S., 1977, Sepsis and congenital asplenia, J. Pediatr. 90: 555.PubMedCrossRefGoogle Scholar
  80. Wargon, L. B., and Lozzio, B. B., 1974, Antibody response to lipopolysaccharide and sheep erythrocytes by congenitally asplenic mice, IRCS 2: 1675.Google Scholar
  81. Wargon, L. B., Lozzio, B. B., and Wust, C. J., 1975, Alteration of bone marrow-thymus cell synergism in hereditarily asplenic and adult-splenectomized mice, Proc. Soc. Exp. Biol. Med. 148: 925.PubMedGoogle Scholar
  82. Welles, W. L., and Battisto, J. R., 1976, Splenic input on immune capability of lymphoid cells, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 157–170, Elsevier/North-Holland, Amsterdam.Google Scholar
  83. Welles, W. L., and Battisto, J. R., 1978, The function of the spleen in immune responses and its influence on other lymphoid organs, in: Animal Models of Comparative and Developmental Aspects of Immunity and Disease (M. E. Gershwin and E. L. Cooper, eds.), pp. 236–249, Pergamon Press, New York.Google Scholar
  84. Welles, W. L., and Battisto, J. R., 1979, Splenic regulation of humoral and cellular immunological responses in other domains, in: The Role of the Spleen in the Immunology of Parasitic Diseases, pp. 59–84, Schwabe, Basel.Google Scholar
  85. Zembala, M., Asherson, G. J., Noworolski, J., and Mayhew, B., 1976, Contact sensitivity to picryl chloride: The occurrence of B suppressor cells in the lymph nodes and spleen of immunized mice, Cell. Immunol. 25: 266.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Wanda Lizak Welles
    • 1
  • Jack R. Battisto
    • 1
  1. 1.Department of Immunology, Research DivisionCleveland Clinic FoundationClevelandUSA

Personalised recommendations