Number of Antibody-forming Cells in Primary and Secondary Reactions after Administration of Antigen

Abstract

WHEN newborn animals are immunized with a bacterial antigen, large quantities of the antigen must be injected to elicit a primary antibody response^1,2. Similarly, if a primary antibody response is induced in newborn rabbits or in sterile piglets by sheep erythrocytes, the amount of antibody in the serum and the number of antibody-forming cells in the spleen are greater the more antigen is used^3,4. In the true primary response, administration of a 75 per cent lethal dose (100 ml. of concentrated suspension of sheep erythrocytes given intraperitoneally to sterile piglets, that is, 2 × 10¹² cells) did not immediately inhibit antibody formation. On the contrary, if the number of cells producing haemolytic 19S and 7S antibodies⁵ is estimated after the intravenous administration to sterile piglets of very large quantities of the antigen (20 ml. of a concentrated suspension of sheep erythrocytes, that is, 4 × 10¹¹ cells), the number of antibody-forming cells in the spleen, where antigen is predominantly localized, is greater than when a similar dose is given sub-cutaneously or intraperitoneally (Fig. 1). The figure shows that the inductive phase—when no antibody-forming cells are detected—lasts 36 h. After this period, there is a rapid increase in the number of antibody-forming cells, at first with a doubling time of 2.6 h, later of 3.3 h. This cannot be considered to result from cell division only. As suggested earlier⁴, it is supposed that the first antibody-forming cells are thought to be formed by differentiation of preformed competent cells and that the rapid increase in the number of antibody-forming cells results from direct asynchronous differentiation of the pre-existing competent cells. The very small number of immunocompetent cells in lymphoid tissue (approximately one cell/10⁶ lymphoid cells) explains the need to use large quantities of the antigen to evoke a true primary reaction in newborn animals. To make possible chance contact between the few immunocompetent cells and a critical quantity of antigen, substantially more antigen is required than in the hypothetical case when numerous competent cells are present (Fig. 2). The number of cells reacting with the antigen during the secondary reaction was found to be greater by at least two orders of magnitude than the number of cells involved in the primary reaction⁶. For simplicity, it is assumed that antigen has the same role in the primary and the secondary reactions. On this assumption, to activate the same number of cells in the secondary as in the primary reaction, the amount of antigen which would suffice would be inversely proportional to the number of reacting cells in lymphoid tissue.