| Abstract: | Newborn rats and mice have rudimentary peripheral lymphoid tissues and are immunologically incompetent. The lymphoid system matures late in the third week after birth, shortly before weaning. The adrenal cortex also is relatively inactive neonatally and begins to secrete glucocorticoids in a mature fashion two weeks after birth. These experiments were designed to test the hypothesis that adrenal glucocorticoids induce maturation of the lymphoid system and immunological competence during the third postnatal week. Mice 10–12 days old were injected daily for 4–11 days with aminoglutethimide, an inhibitor of steroid biosynthesis. The adrenal glands and lymphoid tissues were prepared for histological examination 24 hours after the last injection and evaluated without knowledge of the treatment received. Aminoglutethimide caused adrenal dysplasia with a frequency proportional to dose. Effective doses also inhibited growth, and slightly larger doses were fatal. Therefore it was concluded that large doses of aminoglutethimide caused adrenal insufficiency, but the completeness of this insufficiency in surviving animals was not ascertained. Three phases in postnatal maturation of the lymphoid system were identified by examination of untreated littermate controls and reference to previous work. During the first week after birth, the thymus-dependent lymphoid tissues grow by immigration of thymus-derived cells that soon have the capacity for cell-mediated immunity. During the second postnatal week, a new population of wandering lymphoid cells, presumptively derived from bone marrow, settles in lymphoid organs in response to antigenic stimulation, to form primary lymphoid nodules and a few plasma cells. Late in the third week after birth the machinery for humoral antibody synthesis matures with the appearance of germinal centers and numerous plasma cells, coincident with a great increase in production of immunoglobulin. This third phase of maturation was retarded in mice injected with near-fatal doses of aminoglutethimide. Because these mice suffered neither involution of lymphoid tissue nor suppression of proliferation in thymus or thymus-dependent lymphoid-tissue, it was concluded that the effects of aminoglutethimide upon the development of germinal centers and plasma cells were selective and specific. Therefore these experiments support the hypothesis that glucocorticoid secretion plays a decisive role in maturation of immunological competence during the third week after birth in mice. This role appears to be the potentiation of cellular proliferation and differentiation of B cells in response to antigens, culminating in antibody synthesis. Maturation of adrenal glucocorticoid synthesis has also been implicated in the initiation of physiological involution of the thymus and cessation of intestinal absorption of antibodies during the third postnatal week in rats and mice. |
