Mechanism of Antibody Formation

[摘要] Highly purified diphtheria toxin was trace-labeled with radioactive iodine without measurable loss of its immunological specificity. A detoxified preparation of the labeled material adsorbed to aluminum phosphate gel was inoculated subcutaneously into the footpad of previously immunized guinea pigs. The distribution and catabolism of the antigen at the site of inoculation in the popliteal node and in the blood were determined as a function of time. Control experiments with labeled NaI, di-iodotyrosine and guinea pig albumin were performed in a similar manner.It was found that a reservoir of both the toxoid and the homologous albumin was localized at the site of injection. From there small amounts of protein were continually released to pass through the draining lymph gland and eventually enter the circulation. This pathway was shown to be the main means of protein transport from the skin to the blood.The determinations of antigen-bound radioactivity indicated that the largest per cent destruction of toxoid occurred at the primary locus of antibody formation, the popliteal node. Appreciable catabolism of antigen was also observed in the injection area and in the circulation. In comparison the homologous albumin was not significantly degraded in the skin and lymph tissues, although in the blood it was destroyed at the same rate as antigen, presumably through the normal process of enzymatic breakdown. Since the rates of elimination of albumin and residual toxoid were identical in the tissues examined, it would appear that neither the alum nor local antibodies exerted a specific retention effect on the antigen.When these data were correlated with quantitative measurements of the antibody concentrations in the same tissues, the extent of antigen catabolism in the subcutaneous alum granuloma was shown to be dependent on the available antibody. In the lymph and blood tissues a fraction of the antigen either resisted degradation or was degraded very slowly despite the presence of a large excess of free antitoxin. No direct relationship could be demonstrated between the amount of antigen present in the lymph node and the amount of antibody synthesized. The significance of these results in elucidating the role of the reinjected antigen in both the primary and secondary stimulation of antibody formation is discussed.

[学科分类] 生物科学（综合）