A study of the adoptive secondary response to a protein antigen in mice

Abstract

An attempt has been made to study the cellular inheritance of the induced state of cellular differentiation associated with a secondary immune response. Lymphoid cells have been transferred from donor mice immunized against a protein antigen (bovine gamma globulin) into lethally X -irradiated recipients of the same inbred strain. Evidence is discussed which has led to the assumption that the cells capable of producing a secondary response divide in an irradiated environment. The experiments described here have been designed to show the effect of cell division on the capacity of these cells to produce antibody. The rate of anti­body production in an immune response has been measured by means of the antigen-elimina­tion technique. This technique has been calibrated in passive immunization experiments using an antiserum prepared in outbred mice. The amount of division by the transferred immunized cells before challenge was varied in two ways. First, mice were challenged at different intervals after the transfer of the same number of immunized cells into each recipient mouse. Secondly, different numbers of cells were injected into mice, and these left for a time sufficient for the smallest inoculum used to recolonize the host completely. In the first type of experiment, the results showed that the capacity to produce a secondary response steadily declined with increasing time. Control experiments showed that such a decline can occur after active immunization in non-irradiated mice. In the second type of experiment, the rate of antibody production was directly proportional to the size of the original inoculum of immunized cells. It seems that the rate of antibody production is not increased by cell division. The results are prob­ably, therefore, incompatible with those hypotheses which postulate that all of the mechan­ism responsible for antibody synthesis is capable of replication.