The Role of the Thymus in Development of Immunologic Capacity in Rabbits and Mice

Abstract

Although the thymus gland has been known from antiquity, its role in the body economy has remained enigmatic until recently. During the past year, however, a flurry of reports have given the first indications of the role of this organ in developmental biology. In mammals the thymus develops from the third and fourth pharyngeal pouches in early embryonic life, reaches maximal relative size near the time of birth, and then undergoes a gradual involution. In man the thymus appears in the 10 mm embryo, reaches maximal relative size in the neonate, attains maximal absolute size in the 12-year-old child, and then ..... gradually decreases in relative and absolute size as maturity is reached (1).Our interest in the thymus developed in 1953 when we (2, 3) discovered that a patient with "acquired agammaglobulinemia" had developed a marked immunologic deficiency and an abnormality of the thymus--a benign thymoma--at about the same time. Removal of the thymoma, which was primarily an epithelial stromal overgrowth of the thymus pathologically, failed to alter either the protein abnormality or the immunologic defect. Since that time seven cases of the combined occurrence of these two disorders have been reported (4-8), and in no instance has removal of the thymic tumor restored immunologic function or the protein deficit. Nonetheless, it seems clear that the association of these two rare conditions has been far too frequent to be explained by chance alone.

The early history of B cells

“…Noting the association between acquired agammaglobulinaemia and a thymoma in an adult patient, they thymectomized rabbits only to find no effect on antibody production. However, after learning that early removal of the avian bursa of Fabricius impaired the development of antibody responsiveness, they found that thymectomy of newborn mice and rabbits inhibited lymphocyte development and both cellular and humoral immune responses 22 . Branislav Jankovic and co-workers 23 found that thymectomy of neonatal rats had similar immunological consequences.…”

“…This aborted his experimental plan but led Miller to discover that early thymectomy results in a severe immunodeficiency characterized by marked lymphopenia, inability to reject skin allografts and reduced antibody responses 21 . Good and co-workers 22 followed different clues to discover the importance of the thymus in immune system development. Noting the association between acquired agammaglobulinaemia and a thymoma in an adult patient, they thymectomized rabbits only to find no effect on antibody production.…”

“…Antibodies were shown to mediate humoral immunity 1 Agammaglobulinaemia was described in an immunodeficient patient 11 Early bursectomy was shown to compromise antibody production in birds 13 Early thymectomy was shown to compromise cellular and humoral immunity in mammals 21,22 1890 Antibodies were shown to be γ-globulins 4 Plasma cells were shown to make antibodies 5 The clonal selection theory of antibody production was proposed 16 Circulating lymphocytes were shown to give rise to plasma cells 25,26 Separate B cell and T cell lineages were defined 7 The heavy and light chain composition of antibodies was elucidated 14,15 Boys with congenital agammaglobulinaemia were shown to lack germinal centres and plasma cells 12 Antibody affinity maturation was defined 19 1939 1942 1948 1952 1955 1956 1959 1961 1963 1964 1965 1945 Cells, not serum, were shown to transfer contact sensitivity 8 and delayed-type hypersensitivity 9 1962 1964 One or more lymphocyte lineage? However, this single-lineage model of thymus-derived lymphocytes did not fit well with several observations in birds and patients with immunodeficiency diseases.…”

Antibody‐producing Cells: a Survey of Four Decades of Research Development The Tenth Annual Ernest Witebsky Memorial Lecture, 22 April 1980

“…This period started with the findings by Miller [27] and by Good and collaborators [16] regarding the thymus and the role played by the bursa of Fabricius in the chicken, as found by Glick [15] and further elaborated by Good et al [31]. Neonatally performed thymectomy in mice led to a depression or elimination of cell-mediated immunity.…”

Induction of Abnormal Immunoglobulin Maturation and Antibody Production by Persistent Embryonic Mumps Virus Infection

“…The thymus conditions the development of lymphoid cells necessary Tor antigenic recognition and the initial proliferative phases of cell-mediated immunity (7 10,12,28).…”