Development of immunoglobulin and antibody-synthesizing cells after immunization with different doses of antigen.

The kinetics of development of antibody-synthesizing cells and of cells synthesizing immunoglobulins without detectable antibody function were studied in rats immunized with different doses (0-1, 1, 10, 100 mg) of horse radish peroxidase, bovine serum albumin, human serum albumin, hen ovalbumin, or human IgG, which had been deaggregated or heat-aggregated. Each antigen was injected once or twice as a solution in saline. Antibody and immunoglobulin-producing cells were detected in draining lymph nodes by immunohistochemical staining. In the primary response a few antibody-synthesizing cells were found whatever the dose injected. No increase or some increase was found with the amount of antigen injected, according to the protein used, but with all doses of antigen injected, the population of cells remained small, except with human IgG where a relatively high number of positive cells was detected even after injection of 1 mg of antigen. In the secondary response a few antibody-forming cells were also detected with the lower doses of antigen, but this population increased after boosting with 100 mg of antigen. With human IgG a greater number of positive cells was induced withall the doses tested. A correlation between the number of cells synthesizing immunoglobulins without antibody function and the amount of antigen injected was observed in the primary and secondary responses. The relative size of these two populations varied with the stage of immunity of the animals. In the primary response, the population of cells synthesizing immunoglobulins without antibody function was larger than the population of antibody-forming cells. The same was true in the secondary response, but if after a booster injection the level of antibody-synthesizing cells exceeded that reached in the primary response, the increase of cells synthesizing Ig without antibody function was smaller than the increase in antibody-forming cells. In general the more immunogenic an antigen was, the smaller was the ratio between antibody-forming cells and cells producing immunoglobulin without antibody function.