The Mammalian “Bursa Equivalent”: Does Lymphoid Differentiation Along Plasma Cell Lines Begin in the Gut-Associated Lymphoepithelial Tissues (GALT) of Mammals?

  • Max D. Cooper
  • Alexander R. Lawton


Definition of the induction sites for development of the antibody-producing line of cells in mammals seems to us one of the most important problems in contemporary immunobiology. With the discovery in the early 1960s of the role of the mammalian thymus in the development of immunocompetent cells (Good and Gabrielsen, 1964), it was tempting to assume that the thymus was also central to development of antibody-producing cells. This idea was particularly attractive since deficient antibody responsiveness was frequently found in animals subjected to removal of the thymus early in life. Information gained since refuted this possibility and directed attention away from the thymus in the search for the sites of origin of the plasma cell line.


Germinal Center Humoral Immunity Lymphoid Follicle Peripheral Lymphoid Tissue Induction Site 
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  1. Abdou, N. I., and Richter, M., 1970. Cells involved in the immune response. XVIII. Potential hemolysin-forming cells in the sacculus rotundus of the normal adult rabbit. J. Immunol. 104: 1087.PubMedGoogle Scholar
  2. Ackerman, G. A., 1966. The origin of the lymphocytes in the appendix and tonsil iliaca of the embryonic and neonatal rabbit. Anat. Rec. 154: 21.PubMedCrossRefGoogle Scholar
  3. Adler, W. H., Curry, J. H., and Smith, R. T., 1967. Quantitative aspects of early postnatal immunoglobulin polypeptide chain synthesis in the rabbit. In Smith, R. T., Good, R. A., and Miescher, P. A., eds., Ontogeny of Immunity, University of Florida Press, Gainesville, p. 165.Google Scholar
  4. Archer, O. K., Sutherland, D. E. R., and Good, R. A., 1963. Appendix of the rabbit: A homologue of the bursa in the chicken? Nature 200: 337.PubMedCrossRefGoogle Scholar
  5. Archer, O. K., Sutherland, D. E. R., and Good, R. A., 1964. The developmental biology of lymphoid tissue in the rabbit: Consideration of the role of thymus and appendix. Lab. Invest. 13: 259.PubMedGoogle Scholar
  6. Aspinall, R. L., Meyer, R. K., Graetzer, M. A., and Wolfe, H. R., 1963. Effect of thymectomy and bursectomy on the survival of skin homografts in chickens. J. Immunol. 90: 872.PubMedGoogle Scholar
  7. Astaldi, G., Afro, R., Galimberti, A., and Nervi, M. P., (1968). Phytohemagglutinin and human appendiceal lymphocytes. Lancet ii:172.Google Scholar
  8. Bienenstock, J., and Dolezel, J., 1971. Peyer’s patches: Lack of specific antibody-con-taining cells after oral and parenteral immunization. J. Immunol. 106: 938.PubMedGoogle Scholar
  9. Bockman, D. E., and Cooper, M. D., 1971. Fine structural analysis of pinocytosis in lymphoid follicle-associated epithelium in chick bursa and rabbit appendix. Fed. Proc. 30: 511Google Scholar
  10. Brody, T., and Hencin, R., 1969. The immune competence of Peyer’s patch cells. Fed. Proc. 28:309, abst.Google Scholar
  11. Cantor, H., Mandel, M. A., and Asofsky, R., 1970. Studies of thoracic duct lymphocytes of mice. II. A quantitative comparison of the capacity of thoracic duct lymphocytes and other lymphoid cells to induce graft vs. host reactions. J. Immunol. 104: 409.PubMedGoogle Scholar
  12. Chang, T. S., Rheims, M. S., and Winter, A. R., 1957. The significance of the bursa of Fabricius in antibody production in chickens. I. Age of chickens. Poultry Sci. 36: 735.Google Scholar
  13. Chapman, H., Johnson, J., and Cooper, M. D. Ontogeny of immunoglobulin-containing cells and gut-associated lymphoid tissue in the pig. Submitted for publication. Claman, H. N., Chaperon, E. A., and Triplett, R. F., 1966. Thymus-marrow cell com-binations—synergism in antibody production. Proc. Soc. ExptL Biol. Med. 122: 1167.Google Scholar
  14. Clawson, C. C., Cooper, M. D., and Good, R. A., 1967. Lymphocyte fine structure in the bursa of Fabricius, the thymus, and the germinal centers. Lab. Invest. 16: 407.PubMedGoogle Scholar
  15. Cooper, G. N., and Turner, K., 1967. Immunological responses in rats following antigenic stimulation of Peyer’s patches. I. Characteristics of the primary response. Aust. J. Exptl. Biol. Med. Sci. 45: 363.CrossRefGoogle Scholar
  16. Cooper, G. N., and Turner, K., 1969. Development of IgM memory in rats after antigenic stimulation of Peyer’s patches. J. Retie. Soc. 6: 419.Google Scholar
  17. Cooper, M. D., Peterson, R. D. A., and Good, R. A., 1965. Delineation of the thymic and bursal lymphoid systems in the chicken. Nature 205: 143.PubMedCrossRefGoogle Scholar
  18. Cooper, M. D., Peterson, R. D. A., South, M. A., and Good, R. A., 1966. The functions of the thymus system and the bursa system in the chicken. J. Exptl. Med. 123: 75.CrossRefGoogle Scholar
  19. Cooper, M. D., Schwartz, M. M., and Good, R. A., 1966b. Restoration of gamma globu lin production in agammaglobulinemic chickens. Science 151: 471.PubMedCrossRefGoogle Scholar
  20. Cooper, M. D., Perey, D. Y., McKneally, M. F., Gabrielsen, A. E., Sutherland, D. E. R., and Good, R. A., 1966c. A mammalian equivalent of the avian bursa of Fabricius. Lancet I: 1388.PubMedCrossRefGoogle Scholar
  21. Cooper, M. D., Perey, D. Y. E., Gabrielsen, A. E., Dent, P. B., Cain, W. A., and Good, R. A., 1967. Further evidence that Peyer’s patch tissues of mammals are similar to the bursa of Fabricius of birds. Fed. Proc. 26: 752.Google Scholar
  22. Cooper, M. D., Perey, D. Y., Gabrielsen, A. E., Sutherland, D. E. R., McKneally, M. F., and Good, R. A., 1968. Production of an antibody deficiency syndrome in rabbits by neonatal removal of organized intestinal lymphoid tissues. Internat. Arch. Allergy 33: 65.CrossRefGoogle Scholar
  23. Coppola, E. D., DeLuca, F., Kopycinski, C., and Aboul-Enein, A., 1970. Synergistic effect of Peyer’s patches and spleen cells on humoral antibody production. Fed. Proc. 29:700, abst.Google Scholar
  24. Crabb, E. D., and Kelsall, M. A., 1940. Organization of the mucosa and lymphatic structures in the rabbit appendix. J. Morphol. 67: 351.CrossRefGoogle Scholar
  25. Daguillard, F., and Richter, M., 1970. Cells involved in the immune response. XVI. The response of immune rabbit cells to phytohemagglutinin, antigen, and goat anti-rabbit immunoglobulin antiserum. J. Exptl. Med. 131: 119.CrossRefGoogle Scholar
  26. Davie, J. M., and Paul, W. E., 1971. Antigen binding lymphocyte of non-immune guinea pigs: Specificity and immunoglobulin nature of their receptors. Fed. Proc. 30: 587.Google Scholar
  27. Davies, A. J. S., 1969. The thymus and the cellular basis of immunity. Transplant. Rev. 1: 43.PubMedGoogle Scholar
  28. Davies, A. J. S., Leuchars, E., Wallis, V., Marchant, R., and Elliot, E. V., 1967. The failure of thymus-derived cells to produce antibody. Transplantation 5:222.Google Scholar
  29. Dent, P. B., and Good, R. A., 1965. Absence of antibody production in the bursa of Fabricius. Nature 207: 491.PubMedCrossRefGoogle Scholar
  30. DeSousa, M. A. B., Parrott, D. M. V., and Pantelouris, E. M., 1969. The lymphoid tissues in mice with congenital aplasia of the thymus. Clin. Exptl. Immunol. 4: 637.Google Scholar
  31. DiGeorge, A. M., 1965. Discussion of paper by M. D. Cooper et al. J. Pediat. 67: 907.CrossRefGoogle Scholar
  32. DiGeorge, A. M., 1968. Congenital absence of the thymus and its immunologic consequences: Concurrence with congenital hypoparathyroidism. In Bergsma, D., and Good, R. A., eds., Immunologic Deficiency Diseases in Man, The National Foundation, New York, p. 116.Google Scholar
  33. Evans, E. P., Ogden, D. A., Ford, C. E., and Micklem, H. S., 1967. Repopulation of Peyer’s patches in mice. Nature 216: 36.CrossRefGoogle Scholar
  34. Faulk, W. P., McCormick, J. N., Goodman, J. R., Yoffey, J. M., and Fudenberg, H. H., 1970. Peyer’s patches: Morphologic studies. Cell. Immunol. 1: 500.PubMedCrossRefGoogle Scholar
  35. Friedenstein, A., and Goncharenko, I., 1965. Morphological evidence of immunological relationships in the lymphoid tissue of rabbit appendix. Nature 206: 1115.CrossRefGoogle Scholar
  36. Gilmour, D. G., Theis, G. A., and Thorbecke, G. J., 1970. Transfer of antibody produc-tion with cells from bursa of Fabricius. J. Exptl. Med. 132: 134.CrossRefGoogle Scholar
  37. Gitlin, D., 1971. Development and metabolism of the immune globulins. In Kagan, B. M., and Stiehm, E. R., eds., Immunologic Incompetence, Year Book Medical Publishers, Inc., Chicago, p. 3.Google Scholar
  38. Glick, G., Chang, T. S., and Jaap, R. G., 1956. The bursa of Fabricius and antibody production. Poultry Sci. 35: 224.CrossRefGoogle Scholar
  39. Good, R. A., and Gabrielsen, A. E., eds., 1964. The Thymus in Immunobiology, Hoeber-Harper, New York.Google Scholar
  40. Good, R. A., Cain, W. A., Perey, D. Y., Dent, P. B., Meuwissen, H. J., Rodney, G. E., and Cooper, M. D., 1969. Studies on the nature of germinal centers. In Fiore-Donati, L., and Hanna, M. G., Jr., eds., Advances in Experimental Medicine and Biology, Vol. 5: Lymphatic Tissue and Germinal Centers in Immune Response,Plenum Press, New York, p. 33.Google Scholar
  41. Gowans, J. L., and Knight, E. J., 1964. The route of recirculation of lymphocytes in the rat. Proc. Royal Soc. Lond. B 159: 257.CrossRefGoogle Scholar
  42. Hanaoka, M., and Waksman, B. H., 1970. Appendix and yM-antibody formation. II. Distribution of antibody-forming cells after injection of bovine yglobulin in irradiated, appendix-shielded rabbits. Cell. Immunol. 1:316.Google Scholar
  43. Hanaoka, M., Konda, S., and Takiguchi, T., 1967. Histological appearance of lymph nodes of rabbits after thymectomy or appendectomy at birth followed by X-irradiation and injection of antigens. Acta Haematol. Japan 30: 69.Google Scholar
  44. Hanaoka, M., Nomoto, K., and Waksman, B. H., 1970. Appendix and yM-antibody formation. I. Immune response and tolerance to bovine yglobulin in irradiated, appendix-shielded rabbits. J. Immunol. 104: 616.PubMedGoogle Scholar
  45. Hanaoka, M., Williams, R. M., and Waksman, B. H., 1971. Appendix and -TM antibody formation. III. Uptake and distribution of soluble or alum-precipitated bovine 7-globulin injected into the rabbit appendix. Lab. Invest. 24: 31.PubMedGoogle Scholar
  46. Heim, L. R., McGarry, M. P., and Montgomery, J. R., 1970. Histologic and immunologic capacities of parental spleen, lymph node and Peyer’s patch cells in irradiated hybrid mice. Fed. Proc. 29: 827.Google Scholar
  47. Henry, C., Faulk, W. P., Kuhn, L., Yoffey, J. M., and Fudenberg, H. H., 1970. Peyer’s patches: Immunologic studies. J. Exptl. Med. 131: 1200.Google Scholar
  48. Jacobson, L. O., Robson, M. J., and Marks, E. K., 1950. The effect of X-irradiation on antibody formation. Proc. Soc. Exptl. BioL Med. 75: 145.Google Scholar
  49. Jacobson, L. O., Marks, E. K., Simmons, E. L., and Gaston, E. 0., 1961. Immune response in irradiated mice with Peyer’s patch shielding. Proc. Soc. Exptl. Biol. Med. 108: 487.Google Scholar
  50. Jankovid, B. D., and Isvaneski, M., 1963. Experimental allergic encephalomyelitis in thymectomized, bursectomized and normal chickens. Internat. Arch. Allergy 23: 188.CrossRefGoogle Scholar
  51. Jankovid, B. D., and Mitrovid, K., 1967. Antibody-producing cells in the chicken, as observed by fluorescent antibody technique. Folla Biol. 13: 406.Google Scholar
  52. Kincade, P. W., Lawton, A. R., and Cooper, M. D., 1971. Restriction of surface immunoglobulin determinants to lymphocytes of the plasma cell line. J. Immunol. 106: 1421.PubMedGoogle Scholar
  53. Konda, S., and Takiguchi, T., 1967. Immune response and changes in gamma globulins in thymectomized and/or appendectomized rabbits. Acta Haematol. Jap. 30: 85.Google Scholar
  54. Konda, S., and Harris, T. N., 1966. Effect of appendectomy and of thymectomy, with X-irradiation, on the production of antibodies to two protein antigens in young rabbits. J. Immunol. 97: 805.PubMedGoogle Scholar
  55. Lawton, A. R., Aldrete, J., Mage, R. G., and Cooper, M. D. Manuscript in preparation. Matsaniotis, N., Apostolopoulou, E., and Vlachos, J., 1966. Thymic alymphocytosis. Report of a case with normal Peyer’s patches. J. Pediat. 69: 576.CrossRefGoogle Scholar
  56. Matsumura, T., Noro, Y., Nakomoto, Y., and Miyazaki, F., 1968. Development of the lymphoid cell system in human fetus. X II. Internat. Congr. Pediat., Mexico City, abst.Google Scholar
  57. Meuwissen, H. J., Kaplan, G. T., Perey, D. Y., and Good, R. A., 1969a. Role of rabbit gut-associated lymphoid tissue in cell replication. The follicular cortex as primary germinative site. Proc. Soc. ExptL Biol. Med. 130: 300.Google Scholar
  58. Meuwissen, H. J., Gatti, M. D., Teraski, P. I., Hong, R., and Good, R. A., 1969. Treatment of lymphopenic hypogammaglobulinemia and bone marrow aplasia by transplantation of allogeneic marrow New Engl. J. Med. 281: 691.PubMedCrossRefGoogle Scholar
  59. Micklem, H. S., Ford, C. E., Evans, E. P., and Gray, J., 1966. Interrelationships of myeoloid and lymphoid cells: Studies with chromosome-marked cells transfused into lethally irradiated mice. Proc. Royal Soc. Lond. B 165: 78.CrossRefGoogle Scholar
  60. Miller, H. C., and Cudkowicz, G., 1971. Density gradient reparation of marrow cells restricted for antibody class. Science 171: 913.PubMedCrossRefGoogle Scholar
  61. Miller, J., 1966. Immunological competence: Alteration by whole body X-irradiation and shielding of selected lymphoid tissues. Science 151: 1395.PubMedCrossRefGoogle Scholar
  62. Miller, J. F. A. P., and Mitchell, G. F., 1969. Thymus and antigen-reactive cells. Transplant. Rev. 1: 3.PubMedGoogle Scholar
  63. Mitchell, G. F., and Miller, J. F. A. P., 1968. 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. Exptl. Med. 128: 821.CrossRefGoogle Scholar
  64. Perey, D. Y. E., and Good, R. A., 1968. Experimental arrest and induction of lymphoid development in intestinal lymphoepithelial tissues of rabbits. Lab. Invest. 18: 15.PubMedGoogle Scholar
  65. Perey, D. Y. E., Cooper, M. D., and Good, R. A., 1968. Lymphoepithelial tissues of the intestine and differentiation of antibody production. Science 161: 265.PubMedCrossRefGoogle Scholar
  66. Perey, D. Y. E., Cooper, M. D., and Good, R. A., 1968. The mammalian homologue of the avian bursa of Fabricius: I. Neonatal extirpation of Peyer’s patch-type lymphoepithelial tissues in rabbits: Method and inhibition of development of humoral immunity. Surgery 64: 614.PubMedGoogle Scholar
  67. Perey, D. Y. E., Frommel, D., Hong, R., and Good, R. A., 1970. The mammalian homologue of the avian bursa of Fabricius. II. Extirpation, lethal X-irradiation and reconstitution in rabbits. Effects on humoral immune responses, immunoglobulins and lymphoid tissues. Lab. Invest. 22: 212.PubMedGoogle Scholar
  68. Peterson, R. D. A., Cooper, M. D., and Good, R. A., 1965. The pathogenesis of immunologic deficiency diseases. Am. J. Med. 38: 579.PubMedCrossRefGoogle Scholar
  69. Pollard, M., and Sharon, N., 1970. Responses of the Peyer’s patches in germ-free mice to antigenic stimulation. Inf. and Immunity 2: 96.Google Scholar
  70. Rabellino, E., and Grey, H. M., 1971. Immunoglobulins on the surface of lymphocytes. III. Bursal origin of surface immunoglobulins on chicken lymphocytes. J. Immunol. 106: 1418.PubMedGoogle Scholar
  71. Raff, M. C., and Owen, J. J. T., 1971. Thymus-derived lymphocytes: Their distribution and role in the development of peripheral lymphoid tissues of the mouse. Europ. J. Immunol. 1: 27.CrossRefGoogle Scholar
  72. Rubin, E., 1971. The kinetics of cellular proliferation in the bursa of Fabricius. Master’s thesis, University of Alabama in Birmingham, manuscript in preparation.Google Scholar
  73. Schultz, R. D., Dunne, H. W., and Heist, C. E., 1970. Ontogeny of the bovine immune response. Fed. Proc. 29: 699.Google Scholar
  74. Shimizu, Y., and Andrew, W., 1967. Studies on the rabbit appendix. I. Lymphocyte-epithelial relations and the transport of bacteria from lumen to lymphoid nodule. J. Morphol. 123: 231.PubMedCrossRefGoogle Scholar
  75. Silverstein, A. M., and Prendergast, R. A., 1971. The maturation of lymphoid tissue structure and function in ontogeny. In Lindahl-Kiessling, K., Alm, G., and Hanna, M. G., Jr., eds., Advances in Experimental Medicine and Biology, Vol. 12: Morphological and Functional Aspects of Immunity,Plenum Press, New York-London, p. 37.Google Scholar
  76. Stramignoni, A., and Mollo, F., 1968. Development of the lymphoid tissue in the rab- bit’s appendix. A light and electron microscopic study. Acta Anat. 70: 202.PubMedCrossRefGoogle Scholar
  77. Stramignoni, A., Mollo, F., Rua, S., and Palestro, G., 1969. Development of the lymphoid tissue in the rabbit appendix isolated from the intestinal tract. J. Pathol. 99: 265.PubMedCrossRefGoogle Scholar
  78. Stutman, O., and Good, R. A., 1971. Immunocompetence of embryonic hemopoietic cells after traffic to thymus. Transplant. Proc. 3: 923.PubMedGoogle Scholar
  79. Sussdorf, D. H., 1959. Quantitative changes in the white and red pulp of the spleen during hemolysin formation in X-irradiated and nonirradiated rabbits. J. Inf. Dis. 105: 238.CrossRefGoogle Scholar
  80. Sussdorf, D. H., 1960. Repopulation of the spleen of X-irradiated rabbits by tritium-labeled lymphoid cells of the shielded appendix. J. Inf. Dis. 107: 108.CrossRefGoogle Scholar
  81. Süssdorf, D: H., and Draper, L. R., 1956. The primary hemolysin response in rabbits following shielding from X-rays or X-irradiation of the spleen, appendix, liver or hind legs. J. Inf. Dis. 99: 129.Google Scholar
  82. Sutherland, D. E. R., Archer, O. K., and Good, R. A., 1964. Role of the appendix in development of immunologic capacity. Proc. Soc. Exptl. Biol. Med. 115: 673.Google Scholar
  83. Sutherland, D. E. R., McKneally, M. F., Kellum, M. J., and Good, R. A., 1970. A definition of thymic-dependent areas in the peripheral lymphoid tissues of rabbits. Internat. Arch. Allergy 38: 6.CrossRefGoogle Scholar
  84. Thompson, J. H., and Cooper, M. D., 1971. Functional deficiency of autologous implants of the bursa of Fabricius in chickens. Transplantation 11:71.Google Scholar
  85. Thorbecke, G. J., 1960. Gamma-globulin formation and antibody production in vitro. I. Gamma-globulin formation in tissues from immature and normal adult rabbits. J. Exptl. Med. 112: 279.CrossRefGoogle Scholar
  86. Tyan, M. L., and Herzenberg, L. A., 1968. Studies on the ontogeny of the mouse immune systems: II. Immunoglobulin-producing cells. J. Immunol. 101: 446.PubMedGoogle Scholar
  87. Unanue, E. R., Grey, H. M., and Cerottini, J. C., 1971. Interaction of lymphocytes and macrophages with radioactive protein antigens. Fed. Proc. 30: 588.Google Scholar
  88. Warner, N. L., Szenberg, A., and Burnet, F. M., 1962. The immunological role of differ- ent lymphoid organs in the chicken. Aust. J. Exptl. Biol. Med. Sci. 40: 373.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1972

Authors and Affiliations

  • Max D. Cooper
    • 1
  • Alexander R. Lawton
    • 1
  1. 1.Spain Research Laboratories, Departments of Pediatrics and MicrobiologyUniversity of Alabama Medical CenterBirminghamUSA

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