Frequency and avidity of specific antigen binding cells in developing mice

Abstract

In the course of its development, the mouse acquires a large number of lymphoid cells, each committed to make a single type of antibody molecule. Through these molecules, the cells recognize an enormous number of different foreign antigens. In order to analyze the development of the antigen specific cells the binding of diverse antigens by cells in the fetal, neonatal, and adult mouse was compared. Although the numbers of antigen binding cells present in fetuses and young animals were smaller than in adults, no restriction could be detected in the variety of specificites expressed in the fetuses, either with respect to the kinds of antigens bound, or to the range of avidities of binding. Cells specific for each of the 11 antigens tested could be detected in the fetus only in the last 4 days before birth, at which time they appeared both in the liver and in the spleen. In all cases, these cells disappeared from the liver within a day of birth, but continued to increase in number in the spleen until adulthood. Measurements of the numbers of antigen binding cells in single fetal spleens showed no systematic deviation of individual fetuses from this pattern, suggesting that it is an accurate description of the immunological development of individual mice, and not merely the average of highly disparate populations. The distributions of relative avidities with which fetal and adult cells bound antigens were compared for four antigens, and were identical within experimental error in all cases. The proportions of T and B cells in neonatal and adult antigen binding cell populations were also closely similar. These data are consistent with models for the origin of antibody diversity in which the genes coding for the full repertoire of antibodies are generated somatically from a small number of germ line genes during the course of development, in the absence of any strong selection with respect to antigenic specificity. They also suggest that the sharply restricted ability of the neonatal animal to respond to antigenic stimulation is not due to the lack of antigen specific cells, but rather to the absence of mature cells capable of the interactions needed for a full immune response.