The role of lymphocytes in antibody formation V. Transfer of immunological memory to tetanus toxoid: the origin of plasma cells from small lymphocytes, stimulation of memory cells in vitro and the persistence of memory after cell-transfer

Abstract

Immunological memory to tetanus toxoid was transferred to heavily irradiated rats by thoracic duct lymphocytes (TDL) from primarily immunized donors. The recipients gen­erated substantial serum antibody responses when they were challenged with antigen and at the height of the response accumulations of specifically fluorescent plasma cells had developed in the splenic red pulp. When F 1 hybrid TDL were transferred to irradiated parental-strain animals it was possible to determine the origin of the specifically fluorescent cells in the spleen by observing the damage inflicted on them in vitro by alloantisera and com­plement. The analysis showed that all the antibody-forming cells were of donor origin; in morphological terms the experiments established that small lymphocytes develop by differentiation and division into plasma cells. Secondary responses to tetanus toxoid were also observed when TDL were incubated with antigen in vitro , washed thoroughly and then transferred to irradiated animals without further antigenic challenge. These experiments suggested that macrophages were not essential for the induction of the secondary response. Irradiated rats given TDL from immunized donors 4 weeks previously yielded, in turn, TDL capable of transferring immunological memory to further irradiated animals. This implicates long-lived lymphocytes as the carriers of memory. Further, it was shown that the secondary responsiveness conferred on irradiated animals by TDL was not diminished by chronic drainage of cells from a thoracic duct fistula, a procedure which severely depletes recirculating lymphocytes. This phenomenon has also been observed in actively immunized animals. These observations raise the possibility that recirculating memory cells may with­ draw into lymphoid tissue and become sessile for part of their life history.