Newborn rabbits were injected intraperitoneally with a tolerance-inducing dose of labeled radioactive bovine serum albumin. At varying times, 12 hr to 6 wk after injection, tissues were obtained for radioautography. Cellular uptake of antigen appeared confined to the liver, occurring as follows: (1) It became attached initially to erythrocytes in the intravascular system of the liver. (2) Within 1-2 days after injection, it adhered to the cells in extravascular sites where erythropoiesis persisted. (3) Still later. it was associated with hepatocytes. Erythrocytes with adherent antigen were also found in the peripheral blood throughout the period of investigation. The latter finding led to studies of the peripheral erythrocytes of the neonate; membrane properties of these were found unique compared with the adult. It is inferred that erythropoiesis in the liver represents a distinct stage in cellular development. Studies of nonforeign protein, i.e., rabbit serum albumin in neonates, strongly suggested that the erythrocyte-antigen-hepatocyte interaction in the neonate involved a pattern of cellular recognition of foreign protein. Both hematopoiesis and maturation of the liver are discussed as principal factors modulating antigen handling, antibody production, and/or its detection in the neonatal environment that led to the condition commonly defined as "tolerance."

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